International Journal of Medical Sciences

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17 December 2017

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Int J Med Sci 2010; 7(2):94-100. doi:10.7150/ijms.7.94

Research Paper

Factors affecting the long-term response to tacrolimus in renal transplant patients: Pharmacokinetic and pharmacogenetic approach

Paraskevi F. Katsakiori1, Eirini P. Papapetrou2, George C. Sakellaropoulos3, Dimitrios S. Goumenos4, George C. Nikiforidis3, Christodoulos S. Flordellis1

1. Department of Pharmacology, School of Medicine, University of Patras, Rion, Greece
2. Center for Cell Engineering, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center (MSKCC), New York, NY 10065, USA
3. Department of Medical Physics, School of Medicine, University of Patras, Rion, Greece
4. Department of Internal Medicine-Nephrology, School of Medicine, University of Patras, Rion, Greece

Abstract

Background: The aim of our study was to determine the impact of CYP3A5*1 and CYP3A5*3 on the kinetics of tacrolimus in renal transplant recipients.

Material and methods: Forty kidney recipients were selected to participate. Maintenance scheme consisted of tacrolimus, a purine inhibitor and a steroid. CYP3A5 genotyping was performed with PCR and RFLP. Pharmacokinetic model was developed with Linear Regression and General Linear Model repeated measures approach. The impact of sex, CYP3A5*1 allele, age at transplantation, hepatic and renal function on tacrolimus kinetics was examined.

Results: The frequency of CYP3A5*3/*3 and CYP3A5*1/*3 genotype was 35/40 and 5/40, respectively. No CYP3A5*1/*1 was detected. CYP3A5*1 variant was associated with significant lower TAC dose adjusted concentration at 3, 6, 12 and 36 months after transplantation. Hepatic and renal function showed a significant effect on tacrolimus dose adjusted concentration 3 months after transplantation (p=0.000 and 0.028, respectively). Sex did not show a significant impact on tacrolimus kinetics. Carriers of CYP3A5*1 allele had lower predicted measures for tacrolimus dose adjusted concentration and higher predicted measures for volume of distribution.

Conclusion: We proved that CYP3A5*1 carriers need higher tacrolimus dose than CYP3A5*3 homozygotes to achieve the target blood concentration.

Keywords: CYP3A5, general linear models, linear regression, tacrolimus, renal transplantation

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How to cite this article:
Katsakiori PF, Papapetrou EP, Sakellaropoulos GC, Goumenos DS, Nikiforidis GC, Flordellis CS. Factors affecting the long-term response to tacrolimus in renal transplant patients: Pharmacokinetic and pharmacogenetic approach. Int J Med Sci 2010; 7(2):94-100. doi:10.7150/ijms.7.94. Available from http://www.medsci.org/v07p0094.htm