Dose regimens for Chinese adult liver transplant recipients according to the genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in recipients and donors

作者：Zhu, Liqin; Liao, Shasha; Wang, Nan; Ge, Tingyue; Yang, Jianwei; Xu, Gaoqi; Wang, Jianhai; Li, Keqiu; Li, Guang^*

来源：International Journal of Clinical Pharmacology and Therapeutics, 2016, 54(8): 587-596.

DOI：10.5414/CP202490

• dose regimens
• pharmacogenetics
• liver transplant
• CYP2C9
• CYP2C19
• CYP3A5

Objective: Genetic polymorphisms of the P450 2C9 enzyme (CYP2C9), CYP2C19 and CYP3A5 gene are known to affect the metabolism of many drugs applied in liver transplant recipients, such as warfarin, voriconazole, and tacrolimus. The aim of this study was to recommend dose regimens for the liver recipients based on CYP2C9, CYP2C19, and CYP3A5 genotypic combinations of liver transplant recipients and their donors. Methods: 91 adult Han Chinese liver transplant recipients who underwent orthotopic liver transplantation at Tianjin First Central Hospital, China, between 2013 and 2014 were included in this study. CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3 and CYP3A5*3, in both liver recipients and their grafted liver were tested by polymerase chain reaction-restriction fragment length polymorphism. The dose regimens for the liver recipients were recommended based on CYP genotypic combinations of the recipients and their donors. Results: In the liver transplant recipients, the frequencies of CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, and CYP3A5*3 were found to be 2.75%, 4.40%, 0%, 24.18%, and 75.27%, respectively. Allele frequencies were significantly different for CYP2C9*2, CYP2C19*2, and CYP2C19*3 (p < 0.001) when comparing the recipients with Chinese, Eastern Asians and Caucasians populations. Most dose regimens of drugs, especially of immunosuppressive drugs, should be adjusted according to the variant metabolism activity affected by the genetic polymorphisms in both recipients and their grafted liver. Conclusion: The dose regimens would present considerable intra- and inter-patient variability in liver transplant recipients since the genetic polymorphisms of P450 enzyme in their grafted liver might complicate the metabolism of drugs in liver transplant recipients. Giving careful consideration to the CYP genotypic combinations of transplant recipients and donors in clinical dose regimens could optimize outcomes.

• 出版日期2016-8
• 单位天津市第一中心医院; 天津市第三中心医院; 天津医科大学