Effet du polymorphisme du CYP3A5 sur la pharmacocinétique de la cyclosporine chez les transplantés rénaux: Analyse de pharmacocinétique de population

Translated title of the contribution: CYP3A5 polymorphism effect on cyclosporine pharmacokinetics in living donor renal transplant recipients: Analysis by population pharmacokinetics

Joohan Song, Myeong Gyu Kim, Boyoon Choi, Na Young Han, Hwi Yeol Yun, Jeong Hyun Yoon, Jung Mi Oh

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

BACKGROUND: Cyclosporine is often used to prevent allograft rejection in renal transplant recipients. However, cyclosporine has a narrow therapeutic window and large variability in its pharmacokinetics. Individual characteristics and genetic polymorphisms can cause the variation. Hence, it is important to determine the cause(s) of the variation in cyclosporine pharmacokinetics. To our knowledge, this is the first reported population pharmacokinetic study of cyclosporine in living donor renal transplant recipients that considered the genetic polymorphism as a covariate. OBJECTIVE: To build a population pharmacokinetic model of cyclosporine in living donor renal transplant recipients and identify covariates including CYP3A5*3, ABCB1 genetic polymorphisms that affect cyclosporine pharmacokinetic parameters. METHODS: Clinical characteristics and cyclosporine concentration data for 69 patients who received cyclosporine-based immunosuppressive therapy after living donor renal transplantation were collected retrospectively for up to 400 postoperative days. CYP3A5 *1/*3 and ABCB1 C1236T, G2677T/A, C3435T genotyping was performed. A population pharmacokinetic analysis was conducted using a NONMEM program. After building the final model, 1000 bootstrappings were performed to validate the final model. RESULTS: In total, 2034 blood samples were collected. A 1-compartment open model with first-order absorption and elimination was chosen to describe the pharmacokinetics of cyclosporine. A population pharmacokinetic analysis showed that postoperative days, sex, and CYP3A5 genotype significantly affected the pharmacokinetics of cyclosporine. The final estimate of mean clearance was 56 L/h, and the mean volume of distribution was 4650 L. The interindividual variability for these parameters was 22.98% and 51.48%, respectively. CONCLUSIONS: Using the present model to calculate the dose of cyclosporine with CYP3A5 genotyping can be possible for the patients whose cyclosporine concentration is not within the therapeutic range even with therapeutic drug monitoring.

Translated title of the contributionCYP3A5 polymorphism effect on cyclosporine pharmacokinetics in living donor renal transplant recipients: Analysis by population pharmacokinetics
Original languageFrench
Pages (from-to)1141-1151
Number of pages11
JournalAnnals of Pharmacotherapy
Volume46
Issue number9
DOIs
StatePublished - 1 Sep 2012

Keywords

  • Cyclosporine
  • CYP3A5
  • Kidney transplantation
  • Pharmacogenetics
  • Pharmacokinetics
  • Population genetic polymorphism

Fingerprint

Dive into the research topics of 'CYP3A5 polymorphism effect on cyclosporine pharmacokinetics in living donor renal transplant recipients: Analysis by population pharmacokinetics'. Together they form a unique fingerprint.

Cite this