Tacrolimus shows high interindividual variability in pharmacokinetics. It is primarily metabolized by hepatic cytochrome
P450 3A4 and 3A5 (CYP). In this study, we evaluated the influence of recipient CYP3A5 genotypes on the pharmacokinetics
of Tacrolimus in patients after liver transplantation.
Patients after liver transplantation with Tacrolimus maintenance therapy were included to the study. CYP3A5 genotypes of
the recipients were established. Clinical and laboratory data at various time points (1 month, 3 months, 1 year and 3 years after
start of medication with Tacrolimus) were evaluated retrospectively. Doses and trough levels of Tacrolimus were noted and a
screening of all concomitant medications with possible CYP3A5 interaction was performed. SPSS for windows (release 14.0;
SPSS, Inc) was used for statistical analyses. The criterion for statistical significance was p<0.05.
Ninty-two liver transplant recipients participated in the study. CYP3A5 genotypes were successfully determined in all
subjects and did not deviate from the Hardy-Weinberg equilibirum. 86% of the patients carried the CYP3A5 *3/*3 genotype and
were thus classified as CYP3A5 non-expressors. 14% carried the CYP3A5 *1/*3 genotype and were classified as heterozygous
expressors. No homozygous CYP3A5 expressor (*1/*1) was found. Neither Tacrolimus dose nor levels were significantly different
between CYP3A5 expressors and non-expressors at any point of time (p=0.669, p=0.140, p=0.117, p=0.822).
The pharmacokinetic of Tacrolimus in patients after liver transplantation is not influenced by the recipient CYP3A5 genotype.
It is mostly the hepatic metabolism that contributes to the excretion of Tacrolimus. The donor CYP3A5 genotype might be useful
to predict the Tacrolimus pharmacokinetic.
Kniepeiss Daniela has completed her M.D at the Medical University Graz, Austria and performed her fellowship in General Surgery and Subspeciality
Training in Transplantation at the Department of Transplant Surgery, Medical University Graz, Austria. She has published papers in international
journals and is reviewer for international journals. Research interests are reperfusion methods in liver transplantation, early detection of renal
dysfunction in patients after liver transplantation, CYP3A5 genotypes and transplantation in elderly patients. Since 2011 she is leader of the research
unit ?molecular transplantation medicine ?.
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