摘要
目的探讨CYP3A5基因多态性对服用他克莫司的肾移植患者的药代动力学参数的影响。方法选择24例肾移植患者，治疗方案为他克莫司＋霉酚酸酯＋强的松联合用药；CYP3A5基因分型采用PCR法和Pyrosequencing测序法；药代动力学模型采用LR法和GLM法。分析肾移植患者性别、CYP3A5×1等位基因、肾移植时年龄、肝肾功能对他克莫司药代动力学的影响。结果基因型CYP3A5×3／×317例，CYP3A5×1／×36例，CYP3A5×1／×11例。肾移植后14d及1、3、6、12个月时，CYP3A5＊1等位基因与较低的他克莫司剂量调整浓度相关（P值为0．000）；移植术后3个月，肝肾功能与他克莫司的剂量调整浓度相关（P值为0．028）。性别因素对他克莫司药代动力学无明显影响。结论在达到相同目标浓度的情况下，与携带CYP3A5×1基因型的个体相比，CYP3A5×3基因型需要更低的用药剂量。
Objective To investigate the influence of cytochrome P450 3A5 （ CYP3A5 ） polymorphism on the pharmacokinetics of tacrolimus in renal transplant patients. Methods All of 24 recipients were treated with tacrolimus in combination with mycophenolate mofetil and predonisone. The genotype was determined by polymerase chain reaction, and CYP3A5 polymorphism was confirmed by pyrosequencing.LR and GLM methods were used in pharmacokinetics model. Gender, CYP3A5 x 1 allele, age, liver and kidney function were considered in the reserch of the influence on tacrolimus pharmacokinetics. Results There were CYP3A5 x 3/x 3genotypes in 17 cases （ 70.8% ） , 1/3 in 6 cases （ 25% ） and x 1/x 1 in 1 case （ 4.2% ） identified in 24 renal recipients. CYP3A5 x 1 genotype was related with lower dosage and the adjusted concentration oftacrolimus 14 days, 1 month, 3 months, 6 months, 12 months after renal transplant. Renal and liver function have significant difference with dosage and the adjusted concentration of tacrolimus 3 months after transplant （ P=0.000, P=0.028 ） .Gender has no influence on the pharmacokinetics of tacrolimus. Conclusion To achieve same target concentration, patients with CYP3A5 x 3 genotype need lower tacrolimus dosage than CYP3A5 x 1 genotype.
出处
《浙江临床医学》
2012年第10期1175-1178,共4页
Zhejiang Clinical Medical Journal
