Impact of CYP3A5 genetic polymorphisms and steroids dosing on trough concentration to dose ratio of tacrolimus in Thai kidney transplantation populations
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Abstract
Objective: To determine interaction effect of CYP3A5 genetic polymorphisms and steroids doses on trough concentration (C0) to dose (D) ratio of tacrolimus (C0/D) at 1 month after kidney transplantation by adjusting the influences of age, hemoglobin, and albumin. Methods: Two hundred adult kidney transplant recipients participated in this study. All patients received triple immunosuppressive regimens consisting of oral immediate tacrolimus, mycophenolate mofetil or sodium, and steroids, for one month after kidney transplantation. Interaction effect between CYP3A5 genetic polymorphisms and steroid doses was analyzed using two-way analysis of covariance. Polymorphisms of CYP3A5 was classified into 2 groups: CYP3A5 expressers and non-expressers. Steroids dose was classified into 3 groups: <0.16, 0.16-0.25, and >0.25 mg/kg/day. Results: There was no Interaction effect between CYP3A5 genetic polymorphisms and steroid doses on Log C0/D of tacrolimus (F (2, 192) = 0.859, P= 0.425, ŋp2= 0.009). However, CYP3A5 polymorphisms or steroids doses showed a significant association with Log C0/D of tacrolimus after controlling for ages and hemoglobin (F (1, 192) = 48.492, P< 0.001, ŋp2= 0.202); F (2, 192) = 7.695, P= 0.001, ŋp2= 0.074, respectively). Mean of Log C0/D of tacrolimus in CYP3A5 expressers were lower than those in CYP3A5 non-expressers (1.806, 2.109 (ng/ml)/(mg/kg/day), P< 0.001). The subjects with steroid dose >0.25 mg/kg/day had a lower level of Log C0/D of tacrolimus than those with steroid 0.16-0.25 and <0.16 mg/kg/day, respectively (1.865, 1.938, 2.069 (ng/ml)/(mg/kg/day), P= 0.045, P= 0.003, respectively). Conclusions: One month after kidney transplantation, no interaction effect between CYP3A5 genetic polymorphisms and steroid dose on Log C0/D of tacrolimus was found. CYP3A5 polymorphism is the most importance factors affecting Log C0/D of tacrolimus.
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ผลการวิจัยและความคิดเห็นที่ปรากฏในบทความถือเป็นความคิดเห็นและอยู่ในความรับผิดชอบของผู้นิพนธ์ มิใช่ความเห็นหรือความรับผิดชอบของกองบรรณาธิการ หรือคณะเภสัชศาสตร์ มหาวิทยาลัยสงขลานครินทร์ ทั้งนี้ไม่รวมความผิดพลาดอันเกิดจากการพิมพ์ บทความที่ได้รับการเผยแพร่โดยวารสารเภสัชกรรมไทยถือเป็นสิทธิ์ของวารสารฯ
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