Jia-li Li1, Shu Liu1,2, Qian Fu3, Yu Zhang1,4, Xue-ding Wang1, Xiao-man Liu1, Long-shan Liu3, Chang-xi Wang3, Min Huang1. 1. Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Dong Road, University City, Guangzhou 510006, China. 2. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Dong Road, Guangzhou 510060, China. 3. Kidney Transplant Department, Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou 510080, China. 4. School of Pharmaceutical Sciences, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 510182, China.
Abstract
AIMS: To evaluate the influences of CYP3A4, CYP3A5, MDR1 and NR1I2 polymorphisms on tacrolimus concentration in early postrenal transplant recipients. PATIENTS & METHODS: A total of 159 patients were included, dose-adjusted tacrolimus trough concentration on day 7 after transplantation (C0D7/D) was calculated and 10 SNPs in four genes were genotyped. RESULTS: CYP3A5*3 explained 32.8% of variability of tacrolimus C0D7/D. CYP3A4*1G, MDR1 1236-2677-3435 diplotype and NR1I2 -25385C > T explained 21.4% of variability of tacrolimus C0D7/D in CYP3A5 nonexpressers. CONCLUSION: CYP3A5*3 was the predominant determinant affecting tacrolimus concentration. Genotyping of CYP3A4/MDR1/NR1I2 polymorphisms may be helpful for better guiding tacrolimus dosing in CYP3A5 nonexpressers.
AIMS: To evaluate the influences of CYP3A4, CYP3A5, MDR1 and NR1I2 polymorphisms on tacrolimus concentration in early postrenal transplant recipients. PATIENTS & METHODS: A total of 159 patients were included, dose-adjusted tacrolimus trough concentration on day 7 after transplantation (C0D7/D) was calculated and 10 SNPs in four genes were genotyped. RESULTS:CYP3A5*3 explained 32.8% of variability of tacrolimus C0D7/D. CYP3A4*1G, MDR1 1236-2677-3435 diplotype and NR1I2 -25385C > T explained 21.4% of variability of tacrolimus C0D7/D in CYP3A5 nonexpressers. CONCLUSION:CYP3A5*3 was the predominant determinant affecting tacrolimus concentration. Genotyping of CYP3A4/MDR1/NR1I2 polymorphisms may be helpful for better guiding tacrolimus dosing in CYP3A5 nonexpressers.
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