Population Pharmacokinetics of Cyclosporine in Transplant Recipients
Journal Title: The AAPS Journal - Year 2013, Vol 15, Issue 4
Abstract
A number of classical pharmacokinetic studies have been conducted in transplant patients. However, they suffer from some limitations, for example, (1) the study design was limited to intense blood sampling in small groups of patients during a certain posttransplant period, (2) patient factors were evaluated one at a time to identify their association with the pharmacokinetic parameters, and (3) mean pharmacokinetic parameters often cannot be precisely estimated due to large intraindividual variability. Population pharmacokinetics provides a potential means of addressing these limitations and is a powerful tool to evaluate the magnitude and consistency of drug exposure. Population pharmacokinetic studies of cyclosporine focused solely on developing limited sampling strategies and Bayesian estimators to estimate drug exposure, have been summarized before, and are, therefore, not a subject of this review. The major focus of this review is to describe factors (demographic factors, hepatic and gastrointestinal functions, drug–drug interactions, genetic polymorphisms of drug metabolizing enzymes and transporters) that have been identified to contribute to the large portion of observed variability in the pharmacokinetics of cyclosporine in transplant patients. This review summarizes and interprets the conclusions as well as the nonlinear mixed-effects modeling methodologies used in such studies. A highly diversified collection of structural models, variability models, and covariate submodels have been evaluated and validated using internal or external validation methods. This review also highlights areas where additional research is warranted to improve the models since a portion of model variability still remains unexplained.
Authors and Affiliations
Kelong Han, Venkateswaran C. Pillai, Raman Venkataramanan
Keywords
Related Articles
- EP ID EP681150
- DOI 10.1208/s12248-013-9500-8
- Views 69
- Downloads 0
Pain Assessment in Human Fetus and Infants
In humans, painful stimuli can arrive to the brain at 20–22 weeks of gestation. Therefore several researchers have devoted their efforts to study fetal analgesia during prenatal surgery, and during painfu...
Effects of Molecular Weight and Loading on Matrix Metalloproteinase-2 Mediated Release from Poly(Ethylene Glycol) Diacrylate Hydrogels
Herein, we report on continued efforts to understand an implantable poly(ethylene glycol) diacrylate (PEGDA) hydrogel drug delivery system that responds to extracellular enzymes, in particular matrix metalloproteinase-2...
Reversed phase-high performance liquid chromatographic method to measure migration of semivolatile compound, vanillin, in ipratropium bromide inhalation solution
Concluding summary: Proceedings of the AAPS Biotec Open Forum on “Aggregation of Protein Therapeutics”
Effect of Device Design on the In Vitro Performance and Comparability for Capsule-Based Dry Powder Inhalers
The online version of this article (doi:10.1208/s12248-012-9379-9) contains supplementary material, which is available to authorized users.