1. Effects of CYP3A5 Genetic Polymorphism on the Pharmacokinetics of Tacrolimus in Renal Transplant Recipients.
- Author
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Mac Guad R, Zaharan NL, Chik Z, Mohamed Z, Peng NK, and Adnan WA
- Subjects
- Adult, Aged, Asian People genetics, Dose-Response Relationship, Drug, Female, Genotype, Humans, Malaysia, Male, Middle Aged, Retrospective Studies, Cytochrome P-450 CYP3A genetics, Immunosuppressive Agents pharmacokinetics, Kidney Transplantation, Polymorphism, Genetic, Tacrolimus pharmacokinetics
- Abstract
Background: The aim of this study was to compare the within-patient variability trough levels (Co), dose-adjusted Co, and dose requirements of Prograf and Advograf with CYP3A5 polymorphisms in Malaysia renal transplant recipients., Methods: Stable post-renal transplantation patients switched from Prograf to Advograf were retrospectively identified from University Malaya Medical Centre (n = 28). Co and concomitant tacrolimus dose 6 months preconversion and postconversion were examined. CYP3A5 was genotyped using reverse transcriptase polymerase chain reaction. Wilcoxon signed rank test and Mann-Whitney U test were used to compare Co and dose between formulations and according to genotypes., Results: There was a significant difference in the whole-blood tacrolimus Co between the 2 groups (6.16 ± 1.74 ng/mL vs 4.90 ± 1.06 ng/mL; P = .0001). The mean daily maintenance dose of Prograf was 3.9 ± 2.0 mg/kg (0.06 mg/kg/d), which was reduced to 3.3 ± 1.7 mg/d (0.04 mg/kg/d) with Advograf (P = .01). The mean maintenance dose of tacrolimus required for those with CYP3A5*1/*1 (high-expressive) was significantly higher than those with CYP3A5*1/*3 (intermediate-expressive) and CYP3A5*3/*3 (low-expressive) (P < .01) for both formulations. Comparing those with CYP3A5*1/*1, the average dose-adjusted Co was significantly higher in patients with CYP3A5*3/*3 with Advograf (P < .05)., Conclusions: The requirement for daily maintenance dose was higher in those with CYP3A5*1/*1 variants in both tacrolimus formulations in the Malaysian patients. Furthermore, those with CYP3A5*3/*3 demonstrated significantly higher dose-adjusted Co with Advograf., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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