Effects of CYP3A5 Genetic Polymorphism on the Pharmacokinetics of Tacrolimus in Renal Transplant Recipients

• Published in: Transplantation proceedings Vol. 48; no. 1; pp. 81 - 87
• Main Authors: Mac Guad, R, Zaharan, N.L, Chik, Z, Mohamed, Z, Peng, N.K, Adnan, W.A.H.W.M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2016
• Subjects: Adult; Aged; Asian Continental Ancestry Group - genetics; Cytochrome P-450 CYP3A - genetics; Dose-Response Relationship, Drug; Female; Genotype; Humans; Immunosuppressive Agents - pharmacokinetics; Kidney Transplantation; Malaysia; Male; Middle Aged; Polymorphism, Genetic; Retrospective Studies; Surgery; Tacrolimus - pharmacokinetics
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2016.01.001

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.