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目的研究CYP3A5*3基因多态性在指导肾移植术后他克莫司(FK506)个体化用药的临床应用价值。方法在术前1～2周内采用焦磷酸测序法测定肾移植受体CYP3A5基因型。随机将83例患者分为实验组和对照组,实验组根据CYP3A5基因型的不同调整肾移植术后FK506的初始剂量[表达型为0.15mg/(kg·d),不表达型为0.075mg/(kg·d)],对照组按照传统的给药剂量[0.10mg/(kg·d)]。比较两组肾移植术后7d内达到目标血药浓度范围[(6～10)ng/mL]的百分比、需调整药物剂量的百分比以及3个月内急性排斥反应和药物不良反应(神经毒性、高血脂、高血糖等)发生率之间的差异。结果肾移植术后7d内实验组达到目标血药浓度范围百分比显著高于对照组(62.5% vs 32.6%,P<0.05),而实验组需要调整剂量的百分比显著低于对照组(35.0% vs 65.1%,P<0.05)。实验组和对照组肾移植术后3个月内急性排斥反应发生率分别为20.0%和25.6%,不良反应发生率分别为12.5%和18.6%,实验组较对照组低,但两者比较尚无明显统计学差异(P>0.05)。结论根据CYP3A5*1/*3基因型调整FK506初始用量,优于传统的标准体重剂量给药方案,能有效地使各基因型患者在肾移植术后早期迅速达到有效血药浓度范围。
Objective To investigate the clinical value of CYP3A5 * 3 gene polymorphism in guiding individualized use of tacrolimus (FK506) after renal transplantation. Methods The genotypes of renal transplant recipient CYP3A5 were determined by pyrosequencing within 1 to 2 weeks before operation. Eighty-three patients were randomly divided into experimental group and control group. The experimental group adjusted the initial dose of FK506 [expression 0.15mg / (kg · d)] and non-expression type 0.075mg / (kg · d) after kidney transplantation according to the CYP3A5 genotype. (kg · d)], the control group according to the traditional dose [0.10mg / (kg · d)]. To compare the percentage of target plasma concentrations [(6 ~ 10) ng / mL] within 7 days after renal transplantation, the percentage of drug doses and the acute rejection and adverse drug reaction (neurotoxicity, High cholesterol, high blood sugar, etc.) the difference between the incidence. Results The percentage of target blood concentration in the experimental group reached a significant level within 7 days after renal transplantation (62.5% vs 32.6%, P <0.05), but the percentage of adjusted dose in the experimental group was significantly lower than that of the control group (35.0% vs 65.1%, P <0.05). The incidence of acute rejection in experimental group and control group within 3 months after renal transplantation was 20.0% and 25.6% respectively, and the incidence of adverse reactions were 12.5% and 18.6% respectively. The experimental group was lower than the control group No significant difference (P> 0.05). Conclusion Adjusting the initial dose of FK506 according to the CYP3A5 * 1 / * 3 genotype is superior to the traditional standard body weight dosing regimen, which can effectively reach the effective plasma concentration range in early stage after kidney transplantation for all genotypes.