RESUMEN
Drug interactions between anti-tuberculosis and immunosuppressive medications after renal transplantation are a common problem in Myanmar. The efficacy of both types of drugs can be reduced during the treatment period, which can lead to graft failure and flare-ups of infection. Drug adjustments, with frequent monitoring and close follow-up, are crucial in this period. Ketoconazole decreases tacrolimus metabolism by inhibiting cytochrome P450-3A5 enzymes and P-glycoprotein. It is cost effective and has been frequently used to reduce the dose and cost of tacrolimus. Here, we report the case of a 56-year-old male renal transplant recipient with anti-tuberculosis medications.
RESUMEN
Background: Renal transplant is an effective treatment option for end-stage kidney disease and tacrolimus is one of the most commonly used immunosuppressant drugs in renal transplant patients. Tacrolimus is a substrate of cytochrome P450 3A5 (CYP3A5), and a narrow therapeutic index and large inter-individual variability. The objective of this study was to determine the frequency of CYP3A5*3 polymorphism and its effect on the pharmacokinetics of tacrolimus in post-renal transplant patients at Mandalay General Hospital. Methods: Three different genotypes of CYP3A5 were determined by polymerase chain reaction-restriction fragment length polymorphism in 54 post-renal transplant recipients. Tacrolimus trough concentrations (Ctrough) were measured by enzyme multiplied immunoassay technique following method validation. The apparent clearance (CL/F) was calculated from measured Ctrough. Results: The frequency of CYP3A5*1 allele was 0.24 and that of CYP3A5*3 allele was 0.76 in the study sample. There were a total of 33 CYP3A5 non-expressors (patients with CYP3A5*3/*3 genotype) and 21 CYP3A5 expressors (patients with CYP3A5*1/*1 or CYP3A5*1/*3 genotype), respectively. CL/F was significantly lower in the non-expressor group than in the expressor group (mean±standard deviation, 12.53±5.28 vs. 21.22±5.95 L/hr; P<0.001). The mean Ctrough and concentration dose ratio (C/D) for tacrolimus in CYP3A5 non-expressors were significantly higher than those in CYP3A5 expressors (Ctrough, 7.14±2.56 vs. 5.92±1.76 ng/mL; C/D, 6.92±4.11 vs. 2.89±1.85 ng/mL/mg), respectively (P<0.05). Conclusions: In this study, 76% of the Myanmar renal transplant recipients carried the CYP3A5*3 allele that was associated with lower functional activity of the CYP3A5 enzyme a lower CL/F of tacrolimus in these Thus, CYP3A5 polymorphism influences the pharmacokinetics of tacrolimus, which may affect the pharmacological response to tacrolimus.
