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

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

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

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. Available from http://www.medsci.org/v07p0094.htm