Cytochrome P450 3A41B as Pharmacogenomic Predictor of Tacrolimus Pharmacokinetics and Clinical Outcome in the Liver Transplant Recipients

Abdulkareem Albekairy; Abdulmalik Alkatheri; Shiro Fujita; Alan Hemming; Richard Howard; Alan Reed; Janet Karlix

doi:10.4103/1319-3767.108484

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Cytochrome P450 3A41B as Pharmacogenomic Predictor of Tacrolimus Pharmacokinetics and Clinical Outcome in the Liver Transplant Recipients

Journal article

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Cytochrome P450 3A41B as Pharmacogenomic Predictor of Tacrolimus Pharmacokinetics and Clinical Outcome in the Liver Transplant Recipients

Abdulkareem Albekairy, Abdulmalik Alkatheri, Shiro Fujita, Alan Hemming, Richard Howard, Alan Reed and Janet Karlix

Saudi journal of gastroenterology, Vol.19(2), pp.89-95

03/01/2013

DOI: 10.4103/1319-3767.108484

PMCID: PMC3632017

PMID: 23481136

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Abstract

Background and Aims: Tacrolimus is a macrolide immunosuppressant used for prevention of allograft rejection in organ transplantation and metabolized in the liver and intestine by cytochrome P450 3A4 (CYP3A4) enzyme. A single nucleotide polymorphism (SNP) in the CYP3A4 promoter region has been identified. It has been shown that the presence of CYP3A4*1B allele (variant GG) is associated with a reduced catalytic activity of CYP3A4 in vivo. The aim of this study was to determine the role of CYP3A4*1B on tacrolimus dosing and clinical outcome in liver transplant recipients. Subjects and Methods: Forty-eight liver transplant recipients were stratified according to the genotype. There were 32 wild-type (AA) patients and 5 homozygous variant (GG) and 11 (AG) heterozygous. Tacrolimus doses and trough concentrations as well as phenotypic data were collected in the first 10 days of the transplant. Results: The tacrolimus concentration was significantly higher in the wild (AA) group as compared to homozygous variant (GG) and heterozygous (AG) patients. Homozygous variant (GG) group had significantly lower dose requirements. However, no significant difference was observed in the concentration/dose ratio between all groups. Conclusions: Based on our results, it may be concluded that CYP3A4*1B of recipient is an important factor influencing pharmacokinetic of tacrolimus, as patients with CYP3A4*1B polymorphism may require lower tacrolimus doses to maintain therapeutic levels. The dose reduction may not affect clinical outcomes after liver transplant.

Gastroenterology & Hepatology

Life Sciences & Biomedicine

Science & Technology

Details

Title: Subtitle: Cytochrome P450 3A41B as Pharmacogenomic Predictor of Tacrolimus Pharmacokinetics and Clinical Outcome in the Liver Transplant Recipients
Creators: Abdulkareem Albekairy - King Saud bin Abdulaziz University for Health Sciences
Abdulmalik Alkatheri - King Saud bin Abdulaziz University for Health Sciences
Shiro Fujita - University of Florida
Alan Hemming - University of Florida
Richard Howard - University of Florida
Alan Reed - University of Florida
Janet Karlix - University of Florida
Resource Type: Journal article
Publication Details: Saudi journal of gastroenterology, Vol.19(2), pp.89-95
DOI: 10.4103/1319-3767.108484
PMID: 23481136
PMCID: PMC3632017
NLM abbreviation: Saudi J Gastroenterol
ISSN: 1319-3767
eISSN: 1998-4049
Publisher: MEDKNOW PUBLICATIONS & MEDIA PVT LTD
Number of pages: 7
Language: English
Date published: 03/01/2013
Academic Unit: Accounting; Surgery
Record Identifier: 9984322818502771

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