Effects of CYP3A5 genotypes, ABCB1 C3435T and G2677T/A polymorphism on pharmacokinetics of Tacrolimus in Chinese adult liver transplant patients
Authors: Yuan Zhang
YanWen Zhang
LiQin Zhu
YaQing Jing
Guang Li
JianWei Yang
Journal: Xenobiotica (2015)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: ABCB1 C3435T; CYP3A5; G2677T/A; liver transplant; tacrolimus.
Affiliations: a Department of Pharmacy , Tianjin First Central Hospital , Tianjin , China and.

Abstract:  1. The purpose of this study was to establish a population pharmacokinetic (PK) model of tacrolimus and evaluate the influence of clinical covariates, including the genetic polymorphisms of the cytochrome P450 3A5 gene (CYP3A5) and gene-encoding P-glycoprotein (ABCB1), on the PK parameters in Chinese adult liver transplant recipients. 2. Details of drug dose, sampling times and concentrations were collected retrospectively from routine therapeutic drug monitoring data early after liver transplant. Tacrolimus PKs was studied by a non-linear mixed-effect modeling (NONMEM) method. CYP3A5 genotypes, ABCB1 C3435T and G2677T/A polymorphism and a number of clinical covariates were tested for their influence on TAC PKs. 3. A one-compartment model with first-order absorption and elimination adequately described the data. Apparent clearance (CL/F) and apparent volumes of distribution (V/F) in final population model were 17.6 L/h and 225 L, respectively. The absorption rate constant (Ka) was fixed at 4.48 h(-1). The inter-individual variability in CL/F and V/F was 53.9 and 68%, respectively. In the final model, CYP3A5 genotype, post-operative day, alanine aminotransferase, total bilirubin, hematocrit and blood urea nitrogen were found to significantly influence the CL/F, whereas POD and HB influence V/F. 4. Population PK analysis of tacrolimus in Chinese adult liver transplant patients resulted in identification of the CYP3A5 genotype, POD, BUN, ALP, HCT, TBIL and HB as significant covariates on the PK parameters of tacrolimus. 

Retracted: No

PubPeer comments:
 2020 Expression of Concern. https: doi.org 10.1080 00498254.2020.1750788 This article refers to: Effects of CYP3A5 genotypes, ABCB1 C3435T and G2677T A polymorphism on pharmacokinetics of Tacrolimus in Chinese adult liver transplant patients Concerns have been raised that the study described in the article did not adhere to ethical guidelines as outlined in the Declaration of Helsinki and the Declaration of Istanbul and guidance from the World Health Organization and the World Medical Association regarding the source of transplanted human organs. Specifically, the British Medical Journal Open (BMJ Open) published an article highlighting many papers in which there is concern that transplanted organs were harvested from executed prisoners in China. In response to these concerns we contacted the authors to clarify the source of the transplanted organs received by the patients described in their study. However, despite multiple attempts to contact the authors and their institutions, no response was received. The Editors of Xenobiotica would like to alert readers of this. We will provide an update if we receive any further information. Xenobiotica publishes research adhering to internationally accepted ethical standards and is committed to upholding the Declaration of Helsinki and Declaration of Istanbul. Taylor Francis endorses the ethics guidelines described by the World Health Organization (WHO) and the World Medical Association (WMA). ,