z-logo
Premium
Population Pharmacokinetics of Tacrolimus in Transplant Recipients: What Did We Learn About Sources of Interindividual Variabilities?
Author(s) -
Campagne Olivia,
Mager Donald E.,
Tornatore Kathleen M.
Publication year - 2019
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1325
Subject(s) - tacrolimus , dosing , medicine , covariate , pharmacokinetics , calcineurin , population , transplantation , cyp3a5 , therapeutic drug monitoring , pharmacology , intensive care medicine , econometrics , biology , biochemistry , environmental health , genotype , economics , gene
Tacrolimus, a calcineurin inhibitor, is a common immunosuppressant prescribed after organ transplantation and has notable inter‐ and intrapatient pharmacokinetic variability. The sources of variability have been investigated using population pharmacokinetic modeling over the last 2 decades. This article provides an updated synopsis on published nonlinear mixed‐effects analyses developed for tacrolimus in transplant recipients. The objectives were to establish a detailed overview of the current data and to investigate covariate relationships determined by the models. Sixty‐three published analyses were reviewed, and data regarding the study design, modeling approach, and resulting findings were extracted and summarized. Most of the studies investigated tacrolimus pharmacokinetics in adult and pediatric renal and liver transplants after administration of the immediate‐release formulation. Model structures largely depended on the study sampling strategy, with ∼50% of studies developing a 1‐compartment model using trough concentrations and a 2‐compartment model with delayed absorption from intensive sampling. The CYP3A5 genotype, as a covariate, consistently impacted tacrolimus clearance, and dosing adjustments were required to achieve similar drug exposure among patients. Numerous covariates were identified as sources of interindividual variability on tacrolimus pharmacokinetics with limited consistency across these studies, which may be the result of the study designs. Additional analyses are required to further evaluate the potential impact of these covariates and the clinical implementation of these models to guide tacrolimus dosing recommendations. This article may be useful for guiding the design of future population pharmacokinetic studies and provides recommendations for the selection of an existing optimal model to individualize tacrolimus therapy.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here