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        Effect of cytochrome P450 3A5 polymorphism on the pharmacokinetics of tacrolimus in renal transplant recipients

        Yi Yi Htun,Nwe Nwe Than,Htar Kyi Swe 대한이식학회 2020 Korean Journal of Transplantation Vol.34 No.1

        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.

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        Posttransplantation tuberculosis management in terms of immunosuppressant cost: a case report in Myanmar

        Phyo Wai Lwin,Yi Yi Htun,Aung Kyaw Myint,Htar Kyi Swe 대한이식학회 2021 Korean Journal of Transplantation Vol.35 No.1

        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.

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