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1
Johns, Gianmarc Grazioli. "Structural requirements for time-dependent and time-independent inhibition of prostaglandin synthase I (COX-1) /." Click here for download, 2007. http://proquest.umi.com/pqdweb?did=1303296611&sid=1&Fmt=2&clientId=3260&RQT=309&VName=PQD.
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Sasane, Rahul Madhukar. "Assessment of the effectiveness of a non-steroidal anti-inflammatory drug (NSAID) algorithm in an integrated healthcare system /." Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.
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Tettey-Amlalo, Ralph Nii Okai. "Application of dermal microdialysis and tape stripping methods to determine the bioavailability and/or bioequivalence of topical ketoprofen formulations." Thesis, Rhodes University, 2008. http://hdl.handle.net/10962/d1003274.
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The widespread acceptance of topical formulations intended for local and/or regional activity has prompted renewed interest in developing a model to determine the bioavailability of drugs in order to establish bioequivalence as a means of evaluating formulation performance of multisource products and also for use during formulation development. Current in vivo techniques such as blister suction and skin biopsy amongst others used to determine the bioavailability and/or bioequivalence of topical formulations are either too invasive to generate appropriate concentration-time profiles or require large numbers of study subjects thereby making the study expensive and time-consuming. Moreover, there are currently no sampling techniques that can demonstrate dermal bioavailability and/or bioequivalence of topical formulations intended for local and/or regional activity. Dermal microdialysis is a relatively new application of microdialysis that permits continuous monitoring of endogenous and/or exogenous solutes in the interstitial fluid. The technique is involves the implantation of semi-permeable membranes which are perfused with an isotonic medium at extremely slow flow rates and collection of microlitre sample volumes containing diffused drugs. Tape stripping, a relatively older technique, has been extensively used in comparative bioavailability studies of various topical formulations. However, due to shortcomings arising from reproducibility and inter-subject variation amongst others, the published FDA guidance outlining the initial protocol was subsequently withdrawn. The incorporation of transepidermal water loss with tape stripping has garnered renewed interest and has been used for the determination of drug bioavailability from a number of topical formulations. Hence the primary objective of this research is to develop and evaluate microdialysis sampling and tape stripping techniques, including the incorporation of the determination of transepidermal water loss, to assess the dermal bioavailability of ketoprofen from topical gel formulations and to develop models for bioequivalence assessment. A rapid UPLC-MS/MS method with requisite sensitivity for the analysis of samples generated from dermal microdialysis was developed and validated which accommodated the microlitre sample volumes collected. An HPLC-UV method was developed and validated for the analysis of samples generated from the in vitro microdialysis and in vivo tape stripping studies. The work presented herein contributes to a growing body of scientific knowledge seeking to develop a model for the determination of bioequivalence of pharmaceutically equivalent topical formulations intended for local and/or regional activity in human subjects.
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Zhu, Genghui. "Nonsteroidal antiinflammatory drugs and apoptosis of human gastric epithelial cells /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20471361.
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Chak, Man-lee Charlotta. "A retrospective study on the effectiveness of anti-ulcer drugs in the prevention of nonsteroidal inflammatory drugs (NSAID)-induced gastrointestinal effects." Click to view the E-thesis via HKUTO, 2004. http://sunzi.lib.hku.hk/hkuto/record/B31971453.
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Butler, Gregory James. "Non-steroidal anti-inflammatory drugs and skin cancer /." [St. Lucia, Qld.], 2005. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe19122.pdf.
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朱耿慧 and Genghui Zhu. "Nonsteroidal antiinflammatory drugs and apoptosis of human gastric epithelial cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31239845.
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Momani, Aiman A. "Assessment of the impact of the West Virginia Medicaid's prior authorization policy for NSAIDs on chronic patients economic and humanistic outcomes /." Morgantown, W. Va. : [West Virginia University Libraries], 1999. http://etd.wvu.edu/templates/showETD.cfm?recnum=847.
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Thesis (Ph. D.)--West Virginia University, 1999.Title from document title page. Document formatted into pages; contains xii, 150 p. : ill. Includes abstract. Includes bibliographical references (p. 124-128).
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Griesbach, Robert Christian. "Approaches to the asymmetric synthesis of non-steroidal anti-inflammatory drugs /." Title page, table of contents and abstract only, 1996. http://web4.library.adelaide.edu.au/theses/09PH/09phg848.pdf.
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Bandara, Bandarage Mahesh Kithsiri Optometry & Vision Science Faculty of Science UNSW. "Investigation and characterisation of antibacterial properties of non-steroidal anti-inflammatory drugs." Awarded by:University of New South Wales. School of Optometry and Vision Science, 2005. http://handle.unsw.edu.au/1959.4/22284.
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Microbial contamination of contact lenses is a significant risk factor leading to adverse responses. Adhesion of microorganisms to a contact lens is the first step in a series of events that leads to contact lens-related infections or inflammation. Recently, some of the non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have the ability to interfere with microbial biofilm formation. In this project, antibacterial properties of commonly used NSAIDs (salicylic acid, sodium diclofenac and ketorolac) were assessed and characterised using biological assays and molecular biological techniques. Salicylic acid, ketorolac and diclofenac reduced adhesion of a range of bacterial species isolated from corneal infection and inflammatory events to contact lenses in a dose-dependent manner. Salicylic acid also decreased the adhesion of Pseudomonas aeruginosa and Staphylococcus epidermidis to human corneal epithelial cells in a dose-dependent manner. Results further demonstrated that NSAIDs had a significant impact on the production of virulence factors such as Type IV pili mediated (twitching) motility, flagella mediated swimming, elastase, protease IV and alkaline protease and affected the production of acylated homoserine lactones of P. aeruginosa. Salicylic acid and ketorolac affect the expression of P. aeruginosa outer membrane proteins. In the presence of the salicylic acid and ketorolac more than 85% of all detectable outer membrane proteins changed and most were down-regulated. Moreover, in the presence of salicylic acid at least five gene products, including Na+ - translocating NADH (Nrq1), choline dehydrogenase (CHDH), a hypothetical protein of unknown function, a gene product with no similarity to any known sequence in the database and a sequence similar to 23S rRNA of P. aeruginosa, were down-regulated. The results of this study clearly demonstrated that NSAIDs have a significant impact on virulence factors and the expression of acylated homoserine lactones by P. aeruginosa. This thesis has illustrated the potential of NSAIDs for preventing bacterial contamination of contact lenses by ocular pathogens and highlights the potential for NSAIDs as antibacterial agents. Therefore, this class of compound should be investigated further for their therapeutic efficacy in vivo.
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Gu, Qing. "Helicobacter pylori and non-steroidal anti-inflammatory drugs in gastric carcinogenesis." Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36589718.
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Ford, Lora Beth. "The effectiveness of valdecoxib on post-endodontic pain." Morgantown, W. Va. : [West Virginia University Libraries], 2005. https://etd.wvu.edu/etd/controller.jsp?moduleName=documentdata&jsp%5FetdId=4032.
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Thesis (M.S.)--West Virginia University, 2005.Title from document title page. Document formatted into pages; contains viii, 59 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 33-38).
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Gu, Qing, and 谷青. "Helicobacter pylori and non-steroidal anti-inflammatory drugs in gastric carcinogenesis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B36589718.
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Chak, Man-lee Charlotta, and 翟敏莉. "A retrospective study on the effectiveness of anti-ulcer drugs in the prevention of nonsteroidal inflammatory drugs (NSAID)-inducedgastrointestinal effects." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B31971453.
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Mantzaris, Debbie 1974. "Investigation of the mechanisms involved in delayed ulcer healing by nonsteroidal anti-inflammatory drugs (NSAIDs)." Monash University, Dept. of Surgery, 2001. http://arrow.monash.edu.au/hdl/1959.1/8095.
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Wong, Chun-yu Benjamin. "Role of Helicobacter pylori and non-steroidal anti-inflammatory drugs in prevention of gastric cancer." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31685493.
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Van, Leeuwen Milco. "Synthetic approaches to nonsteroidal anti-inflammatory agents via the ferrous ion initiated Sâ†Râ†N1-reaction." Thesis, University of East Anglia, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305068.
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Bhandari, Khageshor Venables Barney J. "NSAID effect on prostanoids in fishes prostaglandin E2 levels in bluntnose minnows (Pimephales notatus) exposed to ibuprofen /." [Denton, Tex.] : University of North Texas, 2009. http://digital.library.unt.edu/permalink/meta-dc-11058.
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Diaz-Cruz, Edgar S. "Interrelationships between aromatase and cyclooxygenase-2 and their role in the autocrine and paracrine mechanisms in breast cancer." Connect to resource, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1117117648.
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Su, Tao, and 苏涛. "Time-resolved spectroscopic studies of photo-defluorination and photo-decarboxylation reactions of selected fluoroquinolone antibiotic and nonsteroidal anti-inflammatory drugs." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/195990.
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This thesis aimed to investigate the features and properties of the ground states, transient species and photoproducts involved in the photophysical and photochemical processes for four kinds of drug compounds: lomefloxacin (LF), norfloxacin (NF), tiaprofenic acid (TPA), and flurbiprofen (Fp). The investigation used femtosecond transient absorption (fs-TA), nanosecond transient absorption (ns-TA), UV/Vis absorption spectra (UV/Vis), nanosecond transient resonance Raman (ns-TR2) and nanosecond time-resolved resonance Raman spectroscopy (ns-TR3), as well as density functional theory (DFT) calculations. Although many previous investigations have indicated that photo-defluorination or photo-decarboxylation reactions may account for the phototoxicity for these compounds, detailed information on the mechanisms remains unclear.
In this thesis, the photo-defluorination reaction of LF was explored in neutral water at pH 7.2. The fs-TA results revealed that the lowest lying excited singlet state species (S1) partially decayed into the ground state through fluorescence emission and partially underwent cleavage of the carbon-fluorine bond at position 8 to generate into a singlet aryl cation. Subsequently, intersystem crossing (ISC) allowing the transformation from singlet cation to triplet carbene was observed. Finally, a cyclization reaction with the N-ethyl chain took place for the triplet carbene to generate the final product.
The mechanism underlying NF phototoxicity involves a photo-defluorination reaction in neutral water (pH=7.2). The fs-TA spectra indicated that the S1 underwent efficient ISC to swiftly transform into lowest excited triplet (T1) The ns-TA gained under nitrogen-saturated condition observed a new transient species produced from T1 that was proposed to be a transient species derived from the photo-defluorination reaction involving a SN2Ar* mechanism. The photo-defluorinated product ultimately experienced an ISC process to produce the final product.
The photo-decarboxylation mechanism of TPA was studied in a neutral phosphate buffered solution (PBS). The fs-TA data revealed that S1 went through an efficient ISC to rapidly transform into T1 that then undergoes a photo-decarboxylation reaction to produce a triplet biradical species (denoted as TB3). The ns-TA and ns-TR3 results supplied evidence of the protonation process of TB3 that produces the neutral species (denoted as TBP3) that then decayed through ISC to give rise to the singlet TBP species, which underwent further reaction to make the final product (DTPA).
The photo-decarboxylation reaction of Fp was explored in pure acetonitrile (MeCN). The second excited singlet (S2) went through internal conversion (IC) to decay to S1. Intriguingly, three different pathways for S1 decay co-exist. One pathway is fluorescence emission and the second is an ISC process. The third pathway is the homolysis of the carbon α bond reaction that proceeds to generate two radical species, one being a carboxyl species and the other being the residual, denoted as FpR that was liable to be oxidized under an oxygen-saturated condition to yield a new radical species with the addition of one oxygen molecule which is denoted as FOR that then experienced intramolecular hydrogen transfer (IHT) and dehydroxylation (DHO) to produce the final product.published_or_final_version
Chemistry
Doctoral
Doctor of Philosophy
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Moore, Stephen H. "The effectiveness of rofecoxib on post-endodontic pain." Morgantown, W. Va. : [West Virginia University Libraries], 2002. http://etd.wvu.edu/templates/showETD.cfm?recnum=2308.
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Thesis (M.S.)--West Virginia University, 2002.Title from document title page. Document formatted into pages; contains viii, 51 p. : ill. Includes abstract. Includes bibliographical references (p. 39-42).
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Wong, Chun-yu Benjamin, and 王振宇. "Role of Helicobacter pylori and non-steroidal anti-inflammatory drugs in prevention of gastric cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B31685493.
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Lai, Kam-chuen. "Management of peptic ulcer bleeding the significance of Helicobacter pylori and non-steroidal anti-inflammatory drugs /." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31997156.
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Davis, Brian Robert. "Non-Steroidal Anti-Inflammatory Drug Use in Collegiate Athletes." PDXScholar, 2015. https://pdxscholar.library.pdx.edu/open_access_etds/2477.
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Non-steroidal anti-inflammatory drugs (NSAID) are a class of medications used in the treatment of pain, inflammation, and illness. These medications are common, affordable, and easy to access. For these reasons, NSAIDs are commonly used by athletes of all backgrounds for treating injuries and as ergogenic aids. However, despite these behaviors, NSAIDs have well-documented side effects and the efficacious nature of these medications has been brought into question. Despite this, many athletes continue to use these medications frequently and indiscriminately. It is not known why athletes use these medications in light of their questionable effectiveness and cited adverse effects. Therefore, this study was designed to (1) further investigate the prevalence of NSAID use in collegiate-level athletes, (2) investigate attitudes and behaviors toward the use of NSAIDs cross-tabulated by sport, gender, and competition level, and (3) investigate athletes' general knowledge of NSAIDs.
Subjects for this study included 79 student-athletes (44 male; 25 female) attending Portland State University (PSU). The majority of the athletes started taking NSAIDs before high school (72% of the males and 64% of the females). Thirty-three percent of males and 32% of females reported that they had been taking NSAIDs within the past week. High in-season use of NSAIDs was reported by 52% of the male athletes and 48% of the female athletes, whereas off-season use was reported by 21% and 12% of the males and females, respectively. Cited reasons for NSAID use both in-season and off-season were relief of pain due to injury, prevention, recovery, soreness, and tightness. In total, 83% of males and 76% of females reported obtaining NSAIDs primarily through means other than health-care professionals. With regard to dosage, athletes reported taking NSAIDs based on product directions, instructions of an athletic trainer or perceived pain levels. An overwhelming majority of athletes (83% male; 76% female) were not aware of any side-effects from taking NSAIDs
In summary, this study revealed a pattern of high NSAID use in athletes competing in-season compared to a high prevalence of low NSAID use in athletes off-season. It also revealed a high prevalence of non-prescription NSAID use. Additionally, there was a high prevalence of self-purchasing of NSAIDs, combined with self-medication and a long history of NSAID use. This study also revealed a general lack of knowledge about NSAIDs.
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Lai, Kam-chuen, and 黎錦泉. "Management of peptic ulcer bleeding: the significance of Helicobacter pylori and non-steroidal anti-inflammatory drugs." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B31997156.
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Barrios-Rodiles, Miriam. "Regulation of cyclooxygenase-2 expression in human macrophages." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0033/NQ64507.pdf.
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Hayball, Peter John. "Chirality in clinical pharmacology : studies with ketoprofen /." Title page, contents and abstract only, 1993. http://web4.library.adelaide.edu.au/theses/09PH/09phh413.pdf.
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Thesis (Ph. D.)--University of Adelaide, Dept. of Clinical and Experimental Pharmacology, 1993?Copies of author's previously published articles in back-cover pocket. Includes bibliographical references (leaves 180-205).
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Dairam, Amichand. "An investigation into the neuroprotective properties of the non-steroidal anti-inflammatory agents tolmetin, sulindac and turmeric." Thesis, Rhodes University, 2006. http://hdl.handle.net/10962/d1003230.
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Accumulating evidence suggests that anti-inflammatory agents and antioxidants have neuroprotective properties and may be beneficial in the treatment of neurodegenerative disorders. In the present study, the possible neuroprotective properties of tolmetin, sulindac and turmeric were investigated. The antioxidant effects of tolmetin and sulindac were determined by inducing free radical generation with quinolinic acid (QA), cyanide or iron (II) in rat brain homogenates or primary hippocampal neurons. Tolmetin and sulindac significantly reduce lipid peroxidation and scavenge the superoxide anion. Metal binding studies were conducted to determine whether metal chelation is a possible mechanism through which these agents reduce QA and iron (II)-induced lipid peroxidation. UV/VIS, infrared spectroscopy as well as electrochemical studies show that both agents bind to iron (II) and/or iron (III). Histological examination of the hippocampus showed that pre-treatment of animals with tolmetin or sulindac offers protection against intrahippocampal injections of QA. These agents also attenuate QA-induced apoptosis and reduce the loss of neurons in the hippocampus. The co-incubation of primary hippocampal neurons with the NSAIDS also enhanced cell viability which is significantly reduced by QA. Behavioural studies using a water maze showed that the treatment of animals after QA-induced neurotoxicity reduces QA-induced spatial memory loss. Tolmetin and sulindac also reduced glutathione depletion and protein oxidation in rat hippocampus. Both NSAIDS inhibit liver tryptophan 2,3-dioxygenase activity in vitro and in vivo and subsequently increased hippocampal serotonin levels. However, both NSAIDS also reduce dopamine levels in rat striatum. Tolmetin but not sulindac increased the synthesis of melatonin by the pineal gland. The active components of turmeric known as the curcuminoids were separated using preparative thin layer chromatography (TLC). The purity was confirmed by TLC, NMR and mass spectrometry. The environmental toxin lead, induces lipid peroxidation and reduces primary hippocampal neuronal viability. The co-incubation of the neurons with the curcuminoids significantly reduces lead-induced lipid peroxidation and enhances neuronal cell viability in the presence of lead. Lead-induced spatial memory deficit is also attenuated with curcumin, demethoxycurcumin but not bisdemethoxycurcumin. The curcuminoids also reduce lead-induced hippocampal glutathione depletion and protein oxidation. Metal binding studies show that the curcuminoids bind to lead and is another possible mechanism through which the curcuminoids reduce lead-induced neurotoxicity. The findings of this study indicate a possible role of tolmetin, sulindac and turmeric in neurodegenerative disorders such as Alzheimer’s disease. However, tolmetin and sulindac reduce dopamine levels.
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Chuang, Yung-ping, and 莊蓉萍. "Time-resolved resonance raman and density functional theory studies ofthe photochemistry of (S)-ketoprofen." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40988156.
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Chuang, Yung-ping. "Time-resolved resonance raman and density functional theory studies of the photochemistry of (S)-ketoprofen." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B40988156.
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Chew, Angela Christine. "The anti-proliferative effects of thiazolidinediones and non-steriodal anti-inflammatory drugs on androgen-independent prostate cancer." University of Western Australia. School of Medicine and Pharmacology, 2009. http://theses.library.uwa.edu.au/adt-WU2009.0200.
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[Truncated abstract] In recent years a better understanding of the biology of PPAR , a nuclear transcription factor, has emerged, leading to a resurgence in targeting PPAR for chemotherapy. The family of synthetic PPAR agonists, the thiazolidinediones (TZDs), and non-steroidal anti-inflammatory drugs (NSAIDs) have been implicated in the inhibition of cell proliferation, apoptosis and cell cycle arrest of androgen-sensitive (LNCaP) and androgen-independent (PC-3 and DU145) prostate cancer cells generating much interest in their use for potential curative cancer therapies. In light of the potential use of TZDs and NSAIDs in prostate cancer prevention and their ability to induce inhibitory effects in vitro and in vivo, the first aim of this project was to undertake a comprehensive study of the effects of ciglitazone (TZD) and indomethacin (NSAID) on the androgen-independent prostate cancer cell line DU145, using standardised concentrations and time-points to compare the effects of TZDs and NSAIDs on cell proliferation, cell cycle and apoptosis. Treating the cells with either 10 µM ciglitazone or 10 µM indomethacin resulted in a time-dependent decrease in DU145 cell proliferation. The anti-proliferative effects were found to be in-part attributed to the slowing of cell progression through the G1/S-phase checkpoint of the cell cycle, and in the case of ciglitazone, apoptosis also played a role in its anti-proliferative effects in this cell line. Interestingly, although indomethacin failed to induce apoptosis, its antiproliferative effects were more potent than ciglitazone. The second aim of this project was to further investigate the underlying mechanisms responsible for the anti-proliferative effects of ciglitazone and indomethacin by evaluating their ability to modulate PPAR mRNA and protein expression, and to induce PPAR transcriptional activity. ... In addition, ligandinduced regulation of secreted frizzled related protein 4 (sFRP4) expression, a Wnt/ - catenin antagonists, was investigated. It was demonstrated that both ciglitazone and indomethacin attenuated Wnt/ -catenin signalling via the down-regulation of total - catenin levels within the cells, inhibition or slowing of the translocation of cytoplasmic -catenin into the nucleus and inhibition of cyclinD1 expression An inverse relationship between PPAR and -catenin protein levels was also detected, suggesting that PPAR may directly bind to -catenin itself. sFRP4 expression was transiently upregulated by ciglitazone and indomethacin-treatment, suggesting that the antiproliferative effects of the ligands may be mediated in part through regulation of sFRP4 mRNA and protein levels. In summary, the anti-proliferative effects of ciglitazone and indomethacin on the androgen-independent prostate cancer cell line, DU145, described in this thesis are progressive steps in characterising the role of PPAR in prostate cancer cell proliferation. The identification of indomethacin as a more potent PPAR agonist than ciglitazone represents a novel target for the development of preventative strategies for advanced disease, and the relationship between PPAR and the Wnt/ -catenin signalling pathway provide an insight into the mechanisms involved in the anti-proliferative effects of ciglitazone and indomethacin. Further studies into this relationship would advance help identify novel preventative and curative therapeutic strategies for advanced prostate cancer.
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Menke, Eric R. "The effectiveness of prophylactic etodolac on post-endodontic pain." Morgantown, W. Va. : [West Virginia University Libraries], 1999. http://etd.wvu.edu/templates/showETD.cfm?recnum=484.
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Thesis (M.S.)--West Virginia University, 1999.Title from document title page. Document formatted into pages; contains vii, 62 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 41-44).
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Basson, Erina. "Effect of ultrasound on transdermal permeation of diclofenac and the temperature effects on human skin." Thesis, Stellenbosch : University of Stellenbosch, 2005. http://hdl.handle.net/10019.1/2166.
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Thesis (MScMed (Pharmacology))--University of Stellenbosch, 2005.During the last two decades the effects of ultrasound on the transdermal diffusion of a wide variety of drugs have been extensively investigated. Because there is much uncertainty regarding the efficacy of and mechanisms involved in this mode of permeation enhancement, the objective of the study was to investigate the effect of ultrasound on the transdermal permeation of the nonsteroidal anti-inflammatory drug, diclofenac. For this purpose a dual-stage experimental design and a continuous flow-through diffusion system was used. Therapeutic levels of continuous ultrasound of 3 MHz at an intensity of 2 W/cm2 for 10 min, were used. It was clear from the present study that ultrasound enhanced the permeability of human skin to diclofenac released from a commercially available gel. These results were in contrast with those obtained for ibuprofen in an in vitro study across human skin, but in agreement with those obtained in two in vivo studies of the latter nonsteroidal anti-inflammatory drug. Steady state flux values of diclofenac remained approximately 1.26 times higher than those of controls during the 24 h of the experiment. These observations concurred with those made in two previous in vivo studies. Furthermore, the in vitro flow-through diffusion model was shown to have predictive value as an in vivo method for sonophoresis. Temperature-dependent flux rates for 3H2O across human skin were also studied. The mechanistic effects of ultrasound on the permeability characteristics of human skin have been reported on in a number of studies. Although various mechanisms have been proposed, there is no consensus regarding their relative importance. In addition the temperature-dependent flux changes of 3H2O across human skin were investigated using a continuous flow-through diffusion system. The same ultrasound parameters as in the permeability experiments were used. The results obtained showed that temperature increases of approximately 10 °C occurred following sonication. The flux changes of 3H2O across human skin between 37 °C and 42 °C were shown to be reversible. The results from the present study do not support the sonication-heating theory in which permeability changes in skin are primarily attributed to thermally-induced changes in stratum corneum lipids. It was therefore concluded that the enhancement of diclofenac permeation by sonication could not be adequately explained primarily on a thermal basis.
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Öztürk, Özlem Altuntaş İrfan. "Yaşlı ratlarda selektif ve non selektif cox inhibitörlerinin NMDA reseptör subunitlerine etkisi /." Isparta: SDÜ Tıp Fakültesi, 2006. http://tez.sdu.edu.tr/Tezler/TT00268.pdf.
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Parra, Coca Alexander. "Nanopartículas de carprofen para diferentes vías de administración." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/396655.
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El carprofen (CP), es un antiinflamatorio no esteroideo, con actividad antiinflamatoria, analgésica y antipirética, se utiliza en medicina veterinaria para el tratamiento de patologías de origen agudo y crónico, como osteoarticulares, musculares, osteomusculares, respiratorias y también a nivel perioperatorio.
Actualmente la nanotecnología es aplicada cada vez más en todos los campos de la investigación. Las nanopartículas (NPs) a nivel farmacéutico hacen parte de un gran componente para la encapsulación de fármacos, dentro de estas están las NPs poliméricas que presentan una gran versatilidad debido a que encapsulan y liberan una molécula de forma sostenida, son biodegradables y no tóxicas, además pueden ser utilizadas por diferentes vías de aplicación en función de sus características. El desarrollo y optimización de NPs, debe cumplir con un mínimo de condiciones como un tamaño medio de partícula (TM P), índice de polidispersidad (IP), carga superficial o potencial zeta (ZP) y eficacia de encapsulación (EE) adecuados. Las NPs poliméricas de CP (N Ps-CP) elaboradas presentan las siguientes características: un TM P de 189.5 ± 1.67 nm, un IP de 0.01 ± 0.01, ZP de -22.8 ± 0.66 mV y una EE de 74.70 ± 0.95%. El análisis fisicoquímico confirmó que el CP se encuentra disperso dentro de las NPs. En cuanto a la estabilidad, mediante la liofilización, utilizando un crioprotector y además de someterlas a esterilización permite mantener las NPs-CP I iofi I izadas (L-N Ps-CP) y almacenadas por más tiempo. En la diálisis realizada, el fármaco liberado sigue un modelo cinético de primer orden proporcionando una liberación sostenida de CP. El test in vitro de irritación ocular (Hen'is Egg Test Chorioallantoic Membrane -HET-CAM), permite determinar que las L-N Ps-CP no presenta signos de irritación ocular. El análisis de la permeación ex vivo a través de la córnea de conejo (Nueva Zelanda —NZ-), piel humana, de cerdo y de glándula mamaria de vaca, revela que una concentración suficiente de CP fue retenido en el tejido evitando una excesiva permeación y por tanto que potencialmente llegue a nivel sistémico; los estudios de permeación muestran unos valores de difusión similar entre la piel humana y la porcina y superior para la bovina. Las caracterísiticas de las L-N Ps-CP permiten que puedan ser utilizadas por distintas vías de administración.
Para la aplicación de NPs a nivel ocular el tamaño debe ser inferior a 10 p m, siendo un factor importante para evitar molestias debidas al tamaño. A nivel de la piel el TM P cuanto más pequeño permite una mayor penetración folicular y difusión de la nanoestructura. Cuando son aplicadas por vía intraarticular (IA) el tamaño de
partícula debe ser inferior a 200 nm para evitar la formación de trombos. El test de Draize de tolerancia ocular, confirma que no hay signos de irritación, similarmente para el test de irritación Draize en piel de conejos NZ. Las L-NPs-CP aplicadas tópicamente disminuyen significativamente la inflamación in vivo comparado con el fármaco referencia en el modelo de inducción del edema en oreja de ratón TPA.
Con las L-NPs-CP, se confirma una óptima eficacia y su potencial aplicación en cirugía ocular. En relación a su uso externo, pueden ser útiles para el tratamiento de la inflamación dérmica local.
Se determinó la farmacocinética del CP comercial a una dosis única administrada a nivel IV en conejos NZ, seguido de diez semividas del CP, se administraron las L-NPs-CP por vía IA en el conejo. Las L-NPs-CP demostraron ser adecuadas para la administración parenteral. La biodisponibilidad del CP fue del 58.31%.
Se determinó la concentración total de CP retenido a nivel IA, obteniéndose 0.46 µg/mL después de las 9.25 h en el cartílago articular, el menisco y el líquido sinovial.The CP is a nonsteroidal antiinflammatory used for inflammatory processes and articular analgesics such as, respiratory diseases and during and after surgical procedures. Nanostructured encapsulation of drugs, such as nanoparticles (NPs) polymer systems have great versatility because they sustained release molecule and are biodegradable and non-toxic. The development and optimization of NPs must meet minimum conditions such as the average particle size (Z-ave), polydispersity index (IP), surface charge or zeta potential (ZP) and encapsulation efficiency (EE). The polymeric NPs of CP (NPs-CP) were prepared with the following characteristics: A 189.5 ± 1.67nm TMP, a PI of 0.01 ± 0.01 -22.8 ± 0.66mV ZP and 74.70 ± 0.95 EE%. The physico-chemical analysis confirmed that the CP dispersed within the NPs. The stability by lyophilization, using a cryoprotectant and when subjected to sterilization with gamma irradiation allows NPs to keep lyophilised CP (L-NPs-CP) stored longer. The drug released follows a first order kinetic model. Permeation analysis ex vivo in the rabbit cornea, human skin, pork and bovine udder reveals that a sufficient concentration of CP was retained in the tissue avoiding excessive permeation therefore potentially reaching systemic level. Permeation shows values similar diffusion between human skin and the porcine and bovine superior for. The tests in vitro and in vivo, to determine the L-NPs-CP showed no signs of eye and skin irritation. At the eye level, the NPs allow the drug to remain longer at the level of the cornea. The smaller the skin is, Z-ave is a major follicular penetration and drug diffusion. The L-NPs-CP applied topically significantly decrease inflammation in vivo compared to the reference drug induction model of edema in mouse ear TPA. With L-NPs-CP, optimal efficiency in a potential application for eye surgery and for the treatment of local skin inflammation is confirmed. The bioavailability of CP IA is 58.31%, after single dose administration IA knee of L-NPs-CP in rabbits NZ. The total concentration of CP obtained together in the three types of tissue are: synovial fluid and synovium cartilage 0.46 h 9.25 g/mL.
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Faith, Seth Adam. "Resveratrol (3,5,4' trihydroxy-trans-stilbene) blocks herpes simplex virus replication by affecting a host factor." [Kent, Ohio] : Kent State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=kent1162304949.
Full textAbstract:
Thesis (Ph.D.)--Kent State University, 2006.Title from PDF t.p. (viewed Mar. 11, 2009). Advisor: John J. Docherty. Keywords: herpes simplex, virus, resveratrol, NF-kappaB, NSAID Includes bibliographical references (p. 100-105).
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Bhandari, Khageshor. "NSAID effect on prostanoids in fishes: Prostaglandin E2 levels in bluntnose minnows (Pimephales notatus) exposed to ibuprofen." Thesis, University of North Texas, 2009. https://digital.library.unt.edu/ark:/67531/metadc11058/.
Full textAbstract:
Prostanoids are oxygenated derivatives of arachidonic acid with a wide range of physiological effects in vertebrates including modulation of inflammation and innate immune responses. Nonsteroidal anti-inflammatory drugs (NSAIDs) act through inhibition of cyclooxygenase (COX) conversion of arachidonic acid to prostanoids. In order to better understand the potential of environmental NSAIDS for interruption of normal levels COX products in fishes, we developed an LC/MS/MS-based approach for tissue analysis of 7 prostanoids. Initial studies examining muscle, gut and gill demonstrated that prostaglandin E2 (PGE2) was the most abundant of the measured prostanoids in all tissues and that gill tissue had the highest and most consistent concentrations of PGE2. After short-term 48-h laboratory exposures to concentrations of 5, 25, 50 and 100 ppb ibuprofen, 50.0ppb and 100.0 ppb exposure concentrations resulted in significant reduction of gill tissue PGE2 concentration by approximately 30% and 80% respectively. The lower exposures did not result in significant reductions when compared to unexposed controls. Measured tissue concentrations of ibuprofen indicated that this NSAID had little potential for bioaccumulation (BCF 1.3) and the IC50 of ibuprofen for inhibition of PGE2 production in gill tissue was calculated to be 0.4 µM. Short-term laboratory exposure to ibuprofen did not result in significant alteration of concentrations of PGE2 at environmentally relevant concentrations.
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Machado, de Carvalho Liliana Sofia. "Study of the expression and regulation of the autocrine loop components of the cyclooxygenase pathway and their implication in aspirin exacerbated respiratory disease." Doctoral thesis, Universitat de Barcelona, 2015. http://hdl.handle.net/10803/396213.
Full textAbstract:
Aspirin exacerbated respiratory disease (AERD) is a clinical syndrome characterized by the combination of nasal polyps (NPs), chronic hypertrophic eosinophilic sinusitis, asthma and severity to any medication that inhibits cyclooxygenase (COX)-1 enzymes, namely aspirin and other non-steroidal anti-inflammatory drugs. AERD is characterized by intense inflammation of the respiratory mucosa, with large number of activated tissue eosinophils, mast cells, monocytes, and neutrophils. The persistent inflammation likely contributes to the recurrent development of severe nasal polyposis.
The pathogenesis of AERD is not fully understood and many questions remain unsolved. However, several studies have reported that the pathogenic mechanisms of this condition may be due, at least in part, to a marked imbalance in eicosanoid metabolism, possibly increasing and perpetuating the process of inflammation. A central feature of AERD is its association with a profound overproduction and overresponsiveness to cysteinyl leukotrienes (cys-LTs) occurring concomitantly with a marked underproduction and underresponsiveness to prostaglandin (PG) E2, which result in a disproportion between pro-inflammatory and anti-inflammatory mediators. The downregulation of PG pathways impedes its mediators to participate in the attenuation of pro-inflammatory responses. Recent studies have demonstrated that the pattern of cytokine expression could differentiate patients with AERD and patients with asthma or eosinophilic sinusitis who tolerate aspirin.
We hypothesized that the characteristics of the inflammatory airway milieu (cytokine profile) in AERD is responsible for the deficient expression of EP2 , modifying its capacity to respond to PGE2, resulting in an altered regulation of the autocrine positive loop of the COX pathway that contributes to the exacerbated inflammation and remodeling processes usually present in AERD.
In summary, this study provides evidence supporting the hypothesis that the inflammatory environment in the airways of patients with AERD induces alterations in the expression of EP2. This anomaly alters the induction of interleukin-1 receptor type I (IL-1RI), the main factor receptor responsible for the activation of COX-2 by interleukin (IL)-1β, which, in turn, results in a low production of PGE2 which, associated with the low expression of the EP2 receptor, alters the autocrine feedback loop that regulates the COX pathway. The EP2 receptor plays a central role in the alteration of PGE2 synthesis, since its reestablishment can recover the normal function of the autocrine loop and thereby normalizing the expression and function of all the components that constitute it (IL-1RI, COX-2, microsomal PGE synthase-1 (mPGES-1) and PGE2). The
decrease in the synthesis of PGE2 may contribute to the perpetuation of the eosinophilic inflammation and remodeling processes in the airways of patients who suffer from AERD.La enfermedad respiratoria exacerbada por antiinflamatorios no esteroides (EREA) se caracteriza por la presencia de asma bronquial, rinosinusitis crónica con pólipos nasales e hipersensibilidad a la aspirina y otros antiinflamatorios no esteroides. La inflamación de las vías aéreas en los pacientes con EREA se ha relacionada con diversas alteraciones en el metabolismo del ácido araquidónico (AA) las cuales podrían contribuir al incremento y perpetuación de los procesos inflamatorios. Además, estudios recientes también han demostrado que el perfil de citocinas (sobreexpresión de interferón (IFN)-γ e interleucina (IL)-4) en las vías aéreas, podría tener un papel relevante en la regulación del metabolismo del AA en la EREA. La hipótesis general del estudio establece que las características del entorno inflamatorio de las vías aéreas (perfil de citocinas) en la EREA es responsable de la expresión deficiente del receptor EP2, modificando su capacidad de responder a la PGE2, lo que provoca una alteración en la regulación del bucle de retroalimentación positivo autocrina de la vía de la COX, lo cual contribuye a la inflamación descontrolada y a los procesos de remodelado de las vías aéreas normalmente presentes en la EREA. En suma, este estudio aporta evidencias que soportan la hipótesis de que el entorno inflamatorio en las vías aéreas de los pacientes con enfermedad respiratoria exacerbada por antiinflamatorios no esteroides induce la alteración en la expresión del receptor EP2 de la PGE2. Esta anomalía altera la inducción del receptor tipo I de la interleucina-1 (IL-1RI), principal responsable de la activación de la COX-2 por la citocina IL-1β, lo que, a su vez, da como resultado una baja producción de PGE2 que asociada a la baja expresión de su receptor EP2 altera el bucle de retroalimentación autocrina que regula la vía de la COX. El receptor EP2 juega un papel central en la alteración de la síntesis de la prostaglandina E2 ya que su reparación permite recuperar el funcionamiento normal del bucle autocrino y con ello la normalización en la expresión y funcionamiento de todos los componentes del mismo (IL-1RI, COX-2, PGE sintasa microsomal-1 (mPGES-1) y PGE2). La disminución en la síntesis de PGE2 contribuye a perpetuar la inflamación eosinofílica y el proceso de remodelado de las vías aéreas de los pacientes con enfermedad respiratoria exacerbada por antiinflamatorios no esteroides.
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Tettey-Amlalo, Ralph Nii Okai. "In vitro release of ketoprofen from proprietary and extemporaneously manufactured gels." Thesis, Rhodes University, 2005. http://eprints.ru.ac.za/295/.
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Bhala, Neeraj. "Coxibs and traditional NSAIDs : systematic overviews of the randomised evidence for the effects of traditional non-steroidal anti-inflammatory drugs and selective inhibitors of cyclo-oxygenase-2 on vascular and upper gastrointestinal outcomes." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:2b6d8279-bce1-44bd-84c5-7658723786b2.
Full textAbstract:
Background: Comparative assessments of the vascular and upper gastrointestinal risks of different regimens of non-steroidal anti-inflammatory drugs (NSAIDs) are required. Methods: Meta-analyses were conducted, using individual participant data where possible, of placebo-controlled trials of a selective cyclo-oxygenase [COX]-2 inhibitor ('coxib') or traditional NSAID, or randomised trials of a coxib versus traditional NSAIDs. A prespecified subdivision of traditional NSAID regimens of those with antiplatelet activity (mainly naproxen) and those without (mainly diclofenac) was made. Primary outcomes were major vascular events (MVEs; nonfatal myocardial infarction, nonfatal stroke or vascular death) and upper gastrointestinal complications (UGICs; perforation, obstruction or bleed). Findings: Searches identified 788 trials: 200 comparisons of a coxib vs placebo (88,604 participants, mean follow-up 0.60 years), 206 comparisons of a traditional NSAID vs placebo (43,482 participants, 0.46 years) and 149 comparisons of a coxib vs traditional NSAID (137,466 participants, mean follow-up 0.95 years). Compared to placebo, allocation to a coxib increased the risk of MVEs (rate ratio 1.38, 95% CI 1.14-1.66), vascular mortality (1.58, 1.11-2.24) and UGICs (1.81, 1.17-2.81). Overall, in the population studied, coxibs were associated with three additional major vascular events (one fatal) and two (rarely fatal) upper gastrointestinal complications per 1000 person-years exposure. There was no evidence of heterogeneity by duration of follow-up, coxib type, dose (other than for celecoxib), or patient characteristics, for the primary outcomes. The risk of MVEs for traditional NSAIDs without antiplatelet activity (mostly diclofenac 75mg bd or ibuprofen 800mg tds) were comparable to coxibs (1.40, 1.15-1.72); but the risk of UGICs (1.98, 1.39-2.84) was significantly greater. For traditional NSAIDs with antiplatelet activity (mostly naproxen 500mg bd) there were no significant excess of MVEs (0.84, 0.66-1.08), but UGICs were substantially increased (4.06, 2.85-5.78). Both coxibs and traditional NSAIDs increased risk of hospitalisation for heart failure by about two-fold. Interpretation: The vascular and upper gastrointestinal risks of coxibs and high-dose tNSAID regimens can be predicted, allowing the choice of analgesia to be tailored for particular patients.
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Midroni, Ran. "The effect acetylsalicylic acid and acetaminophen on edema, adrenocorticotropin, and beta-endorphin during orofacial inflammation." 1996. http://catalog.hathitrust.org/api/volumes/oclc/47030234.html.
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Jack, DS. "Characterization of the protein binding of non-steroidal anti-inflammatory drugs in synovial fluid." Thesis, 1990. https://eprints.utas.edu.au/20167/7/whole_JackDamonScott1990.pdf.
Full textAbstract:
The clinical pharmacokinetic properties of NSAID's are markedly influenced by the
affinity and extent of their protein binding properties in plasma and synovial fluid.
Whilst the total level of NSAID is dependent upon concentration and affinity of local
protein, it is the unbound / free fraction that is the species which readily diffuses
between plasma and synovial fluid. The synovial fluid kinetics of the NSAlD's
have received remarkably little attention until recent years, despite the increasing
accumulation of evidence casting doubt on a consistent pharmacokinetic correlation
between plasma concentrations of NSAID's and respective analgesic / anti -
inflammatory activity. This study examined the effect of some physical and
environmental factors on the protein binding of piroxicam and ibuprofen in synovial
fluid.
In this current work, the Amicon MPS-1 ultrafiltration device provided rapid and
consistent separation of unbound NSAID in synovial fluids and HSA solutions.
Radiolabelled piroxicam provided a convenient and relatively simple means of
measuring the free fraction of this drug in synovial fluid using this device, with a
coefficient of variation of 9.8%.
The 2-arylpropionic acids include some marketed and commonly prescribed
NSAID's. They possess a chiral centre, are stereospecific in action and may
undergo metabolic inversion from the inactive R-(-) to the active S-(+) enantiomer.
The prostaglandin inhibitory effect resides with the S-(+) enantiomer, yet with the
exception of S-(+) naproxen, these agents are generally administered as racemic mixtures. The extent of metabolic chiral inversion in man is variable and may be one
very important factor in explaining the variability in response to these agents.Despite
the fact that the enantiomers of the 2-arylpropionic acid NSAID's differ in
pharmacological properties, we are still witnessing articles in the literature that
generate data of a non stereospecific nature.
In order to characterize the protein binding of the enantiomers of the chiral NSAID's
(ibuprofen and ketoprofen) in synovial fluid, a GC/MS assay procedure was
developed that was capable of determining ibuprofen enantiomer concentrations of
2ng/mL with a coefficient of variation of 5_ 10.8% and 7.4% for s-ibuprofen and
r-ibuprofen respectively. The entire procedure (complete in a matter of minutes),
was in marked contrast to the more lengthy methods found in the literature. The
procedure was readily adaptable to allow resolution of ketoprofen enantiomers with
a similar degree of sensitivity.
The free fractions of piroxicam and ibuprofen enantiomers were found to be
markedly dependent upon their respective drug and associated albumin
concentrations in synovial fluid according to pre-determined physical conditions.
Binding of piroxicam was found to be independent of pH at concentrations of drug
and albumin typically found in synovial fluid. There were marked differences in the
extent of binding of ibuprofen enantiomers to human serum albumin (HSA)
solutions, "fatty acid - stripped" HSA solutions, and synovial fluid. The current
studies suggest that caution with interpretation of binding constants determined from
experimental data (in these and similar studies), is essential, as most of the
commonly calculated values are based on saturation functions such as those
described by Scatchard and Klotz. Consideration should also be given to alternative
mathematical functions when interpreting the results of non-saturated binding
studies. As synovial fluid is close to the target tissue where a NSAM's effect is exerted, it is
reasonable to expect its concentration in this fluid to be a better indicator of drug
activity in rheumatic disease than in plasma. However, before an attempt to
correlate synovial fluid NSAID concentration with clinical response can be made,
consideration of the physical and environmental parameters affecting the protein
binding of the whole class of these drugs in synovial fluid may be beneficial.
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Jack, Damon Scott. "The pharmacokinetics of chiral non-steroidal anti-inflammatory drugs in synovial fluid and plasma." Thesis, 1993. https://eprints.utas.edu.au/20279/1/whole_JackDamonScott1994_thesis.pdf.
Full textAbstract:
This research described the pharmacokinetics of free/unbound and total (bound plus
unbound) enantiomers of two commonly prescribed non-steroidal anti-inflammatory drugs
(NSAIDs: ketoprofen and ibuprofen) in the synovial fluid and plasma of patients with
inflammatory and non-inflammatory joint disease.
This was facilitated by the development of enantiomeric assays of sufficient sensitivity to
enable the measurement of the very low levels of non-protein bound drug commonly
encountered in plasma, and synovial fluid. The assays involved formation of a mixed
anhydride of the drug with ethylchloroformate and subsequent conversion to an amide by
reaction with optically active amphetamine. The subsequently formed diastereomers were
separated by gas chromatography/mass spectrometry (GC-MS) using selected ion monitoring
(SIM).
The sensitivity limitations of previous assays (with regard to the intended clinical studies) for
these two drugs were explored, and confirmed the benefits for use of deuterated internal
standards of the respective parent NSAIDs in subsequent GC-MS assays of these drugs. A
practical, speedy and economical means of synthesis of deuterated ketoprofen from its nondeuterated
counterpart (for use as an internal standard), was developed. This method may be
a process worthy of consideration in the synthesis of deuterated internal standards for future
GC-MS assays of similar compounds. The current GC-MS assays were capable of
quantifying ketoprofen (2ng/mL) and ibuprofen (3ng/mL) enantiomers from a 2004 sample
of synovial fluid or plasma, which made them particularly suitable for clinical
pharmacokinetic studies. The clinical studies were conducted in human volunteers with effusions into the knee.
Patients were assessed for functional capacity and severity of disease before being given a
single oral dose of either ketoprofen or ibuprofen. Synovial fluid and plasma levels of
free/unbound and total (bound plus unbound) NSAID enantiomers were determined over 24
hours, after which a number of patients continued twice daily administration of either drug
for up to six months. Chronic-dose patients maintained daily diaries and re-visited the centre at monthly intervals for clinical examination and similar determination of synovial fluid and
plasma NSAID enantiomer levels (6-10 hours post morning dose).
In the single dose studies, the pharmacokineties of total and unbound drug in ketoprofen
patients (n = 10) and ibuprofen patients (n = 5) were examined in synovial fluid and plasma
according to several different models (compartmental, non-compartmental and moment
analysis). The synovial fluid models provided a convenient means for characterising the
transfer of the enantiomers of these drugs to and from synovial fluid. The moment analysis
used to derive one of the models in the current work proved particularly convenient in this
respect, and did not require single or multi-compartmental assumptions common to the other
classic models. The synovial fluid model that provided the poorest fit to the data was a
previously developed model that used total (rather than free) plasma levels of these drugs to
describe transfer of the enantiomers to and from synovial fluid. Pharmacokinetic parameters for ibuprofen enantiomers were generally comparable to the
limited body of information able to be gleaned from previous studies. The mean plasma half
lives for enantiomers of both NSAIDs were considerably longer than indicated by previous
studies. This was most likely due to the combined effect of enhanced sensitivity of the assays
and longer sample collection periods (24 hr instead of 12 hr). This may have facilitated a
better portrayal of the terminal phase of the individual drug enantiomer concentration-time
curves compared to previous studies. Consistent with former studies, there was a general
trend for synovial fluid enantiomer levels of both drugs (though lower than corresponding
plasma levels) to take longer to reach maxima, though once achieved, were shown to persist
for a longer time after dosing than for plasma. This finding agreed with the often observed
phenomena of these NSAIDs being usefully prescribed to patients on a twice daily basis,
despite having relatively short plasma half lives.
The disposition of total ketoprofen in synovial fluid was non-stereoselective, and in
agreement with previous studies. However, an interesting finding in the current ketoprofen
work was the significantly higher level of S(+)- relative to R(-)- enantiomer observed in
unbound synovial fluid concentration-time profiles of study patients. A plausible explanation for this may be related to a greater binding affinity of the R enantiomer relative to the S
enantiomer - a finding suggested by in an in-vitro study some ten years ago, but not observed
in other subsequent studies.
The chronic dose studies were conducted to evaluate some of the difficulties associated with
attempts at correlating the concentration and rate of movement into and out of the joint with
the clinical response or adverse effects experienced by the patient. Disparity between
monthly clinical indicators, global efficacy ratings and pharmacokinetic parameters were
highlighted, and add further weight to the argument that if a simple dose-response
relationship in patients who use these agents were to exist, it may not be as straightforward as
once thought.
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Griesbach, Robert Christian. "Approaches to the asymmetric synthesis of non-steroidal anti-inflammatory drugs / by Robert Christian Griesbach." Thesis, 1996. http://hdl.handle.net/2440/18855.
Full textAbstract:
Bibliography: leaves 159-164.iv, 158 leaves ; 30cm.
This thesis examines routes for the asymmetric synthesis of three members of the nonsteroidal anti-inflammatory class of drugs (NSAIDs) The aryl propanoic acid ibuprofen is synthesized in 96% e.e. Control of stereochemistry is achieved by use of the Sharpless epoxidation reaction, followed by reduction of the product epoxide by complex hydride with assistance by titanium tetraisopropoxide acting as a Lewis acid. The final step is the coupling of an optically active carboxylic acid intermediate with the iso-butyl side chain to give (S)-ibuprofen.
Thesis (Ph.D.)--University of Adelaide, Dept. of Organic Chemistry, 1997?
45
Bichara, Jean Bashir. "Regenerative therapy for osseous defects with and without NSAIDS." 1997. http://catalog.hathitrust.org/api/volumes/oclc/48208831.html.
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Motsko, Stephen Paul Rascati Karen L. "The relationship between Cox-2 inhibitors and cardiovascular risk a retrospective analysis using the Veteran Affairs (VA) database /." 2005. http://repositories.lib.utexas.edu/bitstream/handle/2152/1637/motskos88886.pdf.
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Holt, Kris Edward. "Bioequivalence studies of ketoprofen : product formulation, pharmacokinetics, deconvolution, and in vitro - in vivo correlations." Thesis, 1997. http://hdl.handle.net/1957/33829.
Full textAbstract:
This thesis describes a project to produce controlled release ketoprofen beads for capsules, both at Oregon State University and in an industrial scale-up operation, that are bioequivalent to the commercial product Oruvail. A bead formulation was produced by layering drug and binders in water onto nonpareil sugar seeds in a spray coating apparatus. Ketoprofen beads manufactured in this manner will immediately release their drug content in either an in vitro or an in vivo environment. Industrially produced beads were non-homogeneous in size. Large beads in a coating batch sweep up a disproportional amount of coating material leading to a thicker coating layer and decreased drug release rates. In order to predict the effects of coating modifications, an equation was developed to accurately predict the coating thickness of any material applied to spherical particles of any size. The equation developed is suggested as a replacement for one that has been in published and cited for over 20 years, but overestimates
coating thickness.
The bulk of this thesis details the process of altering the drug release
characteristics of the beads through application of diffusional and enteric barrier coatings, and testing for bioequivalence with Oruvail through biostudy data gathered from human volunteers. Urinary drug excretion rates were measured as a substitute for timed blood sampling of the subjects. Validity of the substitution was shown. Fed state biostudies involved beads manufactured and coated at Oregon State University. Fasted state biostudies involved beads that were industrially manufactured in a scale-up operation and coated both industrially and at Oregon State University.
Deconvolution, a mathematical tool, was used to determine in vivo dissolution rates and the need for further coating modification. Statistical testing using a Two 1-Sided T test was the final arbiter of whether or not bioequivalence
was concluded. Bioequivalence was achieved in subjects under a fed state and finally under fasting conditions, as required by the Food and Drug Administration, with drug beads coated with ethylcellulose to slow drug release and overcoated with an enteric bather to retard early drug release.
Deconvolved in vivo dissolutions originating from biostudy data were used to develop In Vitro / In Vivo Correlations (IVIVC's). IVIVC's were used to predict in vivo biostudy data from in vitro dissolution results following coating formulation modification. A practical guide for the development and use of an IVIVC was written for pharmaceutics practitioners who have an understanding of pharmacokinetics, but may lack sufficient expertise in pharmacokinetics to develop
an IVIVC.Graduation date: 1998
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Kitching, Jacki Anne. "The development of new, non-steroidal anti-asthma drugs with novel modes of action." Phd thesis, 2008. http://hdl.handle.net/1885/151679.
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Olazabal-Bello, Angelita C. "The effect of prophylactic use of oral ketorolac and ibuprofen in the control of endodontic post treatment pain a thesis submitted in partial fulfillment ... for the degree of Master of Science in Endodontics ... /." 1993. http://catalog.hathitrust.org/api/volumes/oclc/68944152.html.
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Motsko, Stephen Paul. "The relationship between Cox-2 inhibitors and cardiovascular risk: a retrospective analysis using the Veteran Affairs (VA) database." Thesis, 2005. http://hdl.handle.net/2152/1637.
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