Littérature scientifique sur le sujet « Sustained release lithium »

SummaryAcute lithium intoxication is potentially lethal. Compared to conventional lithium preparations, sustained-release lithium formulations present specific problems for medical practice in the case of overdose. We report a case of intoxication with 8000 mg of sustained-release lithium carbonate preparation (Teralithe 400 LP®). Twenty-five hours after the ingestion, the patient was still asymptomatic, despite a serum level in the toxic range. After comparison of this case with reports found in the Medline database, we consider the clinical management of such cases.

With increasing energy storage demand, research on high energy density and stable battery became essential. Among different anode materials for lithium batteries, lithium metal is an ideal anode material as it has low redox potential and high specific capacity. Therefore, for post-lithium ion battery with high energy density cannot avoid using lithium metal as an anode. However, lithium metal anode has stability and safety issues due to dendritic growth. Lithium metal in contact with organic electrolyte reacts with the electrolyte to form solid electrolyte interface (SEI). SEI prevents further electrolyte consumption, however presence of unstable SEI causes uneven lithium ion diffusion through the SEI layer and induces lithium dendrite growth. Therefore, uniform deposition of lithium and stable SEI is important to operate lithium metal anode safely. The application of nitrate additives in carbonate electrolyte has been very limited due to poor solubility. However, nitrate containing polymer interlayer can release additive constantly enabling nitrate act as an electrolyte additive. Herein, AgNO3 synthesized with PAN nanofibers (AgPAN) is used as an additive to induce uniform lithium deposition and stable SEI formation. In the symmetric cell test, life time of 20 µm thick lithium foil enhanced from 140 hr to 300 hr with AgPAN. Lithium nucleation overpotential disappeared and overall overpotential is reduced. Originally, plane lithium foil had the sparsely deposited dendrite shaped lithium, but with AgPAN lithium was evenly deposited and grow in spherical shape. Ag+ reduces on lithium metal surface acting as a lithium nucleation seed helping uniform lithium deposition and NO3 - reacts with lithium to form stable inorganic SEI layer (Li2O, Li3N, LiNxOy, and etc) resulting in stable cycling of lithium metal anode.

Abstract Clinically significant delayed absorption after lithium overdose has been reported previously without adequate explanation. We have studied two patients after they took massive intentional lithium overdoses. The first patient presented shortly after ingesting 74 g of lithium carbonate. Pharmacokinetic analysis with a multicompartmental model of 29 serum lithium concentrations during 300 h (including hemodialysis) established absorption and elimination kinetics. Lithium absorption was both slow (peak concentration 33 h after the initial overdose) and delayed (a second peak occurred at 148 h, 30 h after initiation of oral tube feedings). The delayed absorption of a large fraction of lithium implicated a gastrointestinal drug reservoir. Study of the pharmacokinetics in a second patient, who ingested 98 g of lithium carbonate, provided additional evidence of an endogenous reservoir. This patient's medical management was guided by experience gained from the initial case. Appropriate management for a predicted endogenous drug reservoir may have shortened intensive care and hospitalization. In treating overdoses of sustained-release drug preparations, clinically significant delayed absorption triggered by enteral fluids must be considered as a contributor to delayed absorption.

The unusual susceptibility of the Al-Li alloy AA8090 to sustained macroscopic deviation of fatigue cracks from a nominal mode I path during conventional fatigue testing is discussed. It is demonstrated that the mixed mode crack growth associated with macroscopic deviation may be characterized in terms of elastic strain energy release rates for a range of mixed mode loading conditions. It is specifically shown that this form of mixed mode crack growth may lead to non-conservative crack growth predictions when these materials are subjected to conventional, mode I based structure lifing techniques.

Le nombre croissant de patients ayant une maladie chronique, pour la plupart assujettis à la prise d’un traitement au long terme, justifie l’exploration et la caractérisation des facteurs phénotypiques et génétiques de la réponse pharmacologique. L’identification et l’estimation de la variabilité pharmacocinétique-pharmacodynamique impliquée dans la réponse à un traitement sont des étapes indispensables de cette exploration pour aboutir à une médecine de précision. Nous avons étudié la réintroduction des β-bloquants après chirurgie cardiaque dans une cohorte multicentrique prospective conduite chez des patients recevant un traitement chronique par β-bloquants et ayant subi une chirurgie cardiaque. Avec une analyse par landmark, nous avons montré l’efficacité, sur la prévention de la survenue de fibrillation auriculaire, de la réintroduction de β-bloquants 72h après chirurgie cardiaque. Nous avons modélisé, par approche de population, les données de concentration sérique, érythrocytaire et urinaire du lithium à libération prolongé administré en une prise par jour chez des patients bipolaires sous traitement depuis au moins deux ans. Un protocole de recherche clinique a ensuite été rédigé, avec une optimisation des temps de prélèvements, basée sur le modèle pharmacocinétique obtenu, pour caractériser les variabilités inter- et intra-individuelles et identifier les facteurs prédictifs de la réponse prophylactique au lithium. Nous avons évalué, par simulation, l'impact du plan expérimental croisé par rapport au plan parallèle, ainsi que le choix du modèle statistique d’analyse, pour des études pharmacogénétiques évaluant deux traitements (candidat et référence) lorsqu'un polymorphisme génétique augmente ou non l’efficacité du traitement candidat par rapport à la référence. Les résultats de cette étude de simulation montrent que le choix du modèle d'abord, puis le choix du plan expérimental ensuite affectent fortement non seulement l’erreur de type I et la puissance de détecter une interaction gène-traitement, mais aussi l'attribution correcte du traitement. Ces travaux confortent la nécessité d’utiliser des outils statistiques et des plans expérimentaux adéquats dans l’analyse d’un essai clinique ou d’une étude pharmaco-épidémiologique pour caractériser et quantifier la variabilité de la réponse pharmacologique
The increasing number of patients with chronic diseases, most of whom are subject to long-term treatment, justifies the exploration and characterisation of phenotypic and genetic factors of pharmacological response. The identification and estimation of the pharmacokinetic-pharmacodynamic variability involved in the response to a treatment are essential steps in this exploration to achieve precision medicine. We studied the re-introduction of β-blockers after cardiac surgery in a prospective multicentre cohort of patients receiving chronic β-blocker therapy and who underwent cardiac surgery. With a landmark analysis, we have shown the efficacy of reintroducing β-blockers 72 hours after cardiac surgery on the occurrence of atrial fibrillation. We modelled, using a population approach, the serum, erythrocyte and urine concentration data of once-daily sustained-release lithium in bipolar patients undergoing treatment for at least two years. A clinical research protocol was then written, with an optimization of sampling times, based on the pharmacokinetic model obtained, to characterise inter- and intra-individual variability and to identify predictive factors of the prophylactic response to lithium. We evaluated, by simulation, the impact of the crossover versus parallel design, as well as the choice of statistical model during the analysis, in pharmacogenetic studies evaluating two treatments (candidate and reference) when a genetic polymorphism increases or not the efficacy of the candidate treatment compared to the reference. The results of this simulation study show that the choice of the model and the choice of the experimental design strongly affect not only the type I error and the power to detect a gene-treatment interaction, but also the correct allocation of the treatment. This work reinforces the need to use adequate statistical tools and experimental designs in the analysis of a clinical trial or pharmacoepidemiological study to characterize and quantify the variability of the pharmacological response