Predictive value of tacrolimus concentration/dose ratio in first posttransplant week for CYP3A5-polymorphism in kidney-transplant recipients  

作　　者：Pham-Thai Dung Hoang-Xuan Su Nguyen-Chi Tue Nguyen-Huu Ben Nguyen-Minh Phuong Tuan-Ngoc Tran Phan-Ba Nghia Diem-Thi Van Nguyen Thi-Thuy Dung Hoang-Trung Vinh Lionel Rostaing Pham-Quoc Toan 

机构地区：[1]Center of Critical Care Medicine,Emergency and Clinical Toxicology,Military Hospital,Hanoï100000,Viet Nam [2]Institute of Biomedicine and Pharmacy,Vietnam Military Medical University,Hanoï100000,Viet Nam [3]Department of Post-Transplant Intensive Care and Treatment,Center of Organ Transplantation-Military Hospital,Hanoï100000,Viet Nam [4]Department of Occupational Medicine,Vietnam Military Medical University,Hanoï100000,Viet Nam [5]Department of Military Medical Command and Organization,Vietnam Military Medical University,Hanoï100000,Viet Nam [6]Department of Nephrology and Dialysis,Military Hospital,Hanoï100000,Viet Nam [7]Department of Nephrology,Hemodialysis,Apheresis,and Kidney Transplantation,Grenoble University Hospital,Grenoble 38043,Auvergne-Rhone-Alpes,France

出　　处：《World Journal of Transplantation》2025年第2期197-204,共8页世界移植杂志(英文)

基　　金：Supported by the Vietnam National Foundation for Science and Technology Development,No.NAFOSTED 04/2020/TN.

摘　　要：BACKGROUND Tacrolimus(TAC)is metabolized primarily by the CYP3A-encoded enzyme family(CYP3A4,CYP3A5,and CYP3A7).Individuals expressing the CYP3A51 allele are considered fast metabolizers and generally require higher TAC doses to reach therapeutic levels.AIM To evaluate the predictive value of the TAC concentration-to-dose(C0/D)ratio for identifying CYP3A5 poly-morphisms in renal transplant recipients.METHODS Eighty-six de novo kidney transplant recipients with TAC-based immunosuppression from the Department of Nephrology and Dialysis at Military Hospital 103(Hanoi,Vietnam)were included in this retrospective study.Blood samples were collected within the first week post-transplantation to monitor TAC levels and to perform genotyping for CYP3A5 genetic polymorphisms.RESULTS The CYP3A53/3 genotype was identified in 37 patients(43%),CYP3A51/3 in 40 patients(46.5%),and CYP3A51/1 in 9 patients(10.5%).Patients carrying the CYP3A51/3 or CYP3A51/1 genotype,classified as fast metabolizers(CYP3A5 expressers),had significantly lower TAC C0 concentrations and C0/D ratios compared to slow meta-bolizers(CYP3A53/3 genotype)at multiple time points during follow-up(all P<0.001).Notably,the TAC C0/D ratio obtained on day 1(0.91)was shown to predict CYP3A5 polymorphism with a sensitivity of 84.6%and a specificity of 84.6%.CONCLUSION This study demonstrates that the TAC C0/D ratio provides a reliable predictive value for CYP3A5 polymorphisms,which can be used to individualize TAC dosing in renal transplant recipients in Vietnam and other low-income countries.

关 键 词：TACROLIMUS CYP3A5 Renal transplant recipient Concentration-to-dose Kidney transplant 

分 类 号：R699.2[医药卫生—泌尿科学]