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CYP3A5基因型与缓释剂型对中国肾移植术后患者体内他克莫司药动学特征的影响

Impact of CYP3A5 genetic polymorphism and modified release formulation on tacrolimus pharmacokinetics in Chinese renal transplant recipients

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【作者】 陈攀孙萍萍刘晓曼王洪阳李军傅茜陈孝黄民王长希

【Author】 CHEN Pan;SUN Ping-ping;WANG Hong-yang;the First Affiliated Hospital of Sun Yat-sen University;

【机构】 中山大学附属第一医院药学部中山大学临床药理研究所中山大学附属第一医院器官移植中心

【摘要】 目的:研究CYP3A5基因型与缓释剂型对中国肾移植术后患者体内他克莫司药动学特征的影响。方法:采用化学发光免疫法检测20例肾移植术后患者在服用缓释(10例)和普通剂型(10例)他克莫司后的全血浓度;采用聚合酶链反应-限制性片段长度多态法检测服用缓释剂型他克莫司患者的CYP3A5基因型;缓释剂型组检测0~24h的11个时间点,而普通剂型检测0~12h内的10个时间点。结果:无剂量校正的缓释剂型组的AUC0~24h为普通剂型组AUC0~12h的1.78倍,有剂量校正的缓释剂型组的C0为普通剂型的60%,其余药动学参数无显著性差异;缓释剂型中慢代谢型组的Cmax、AUC0~24h和C0分别为快代谢型组的1.75、1.96、2.49倍(无剂量校正)以及1.80、2.34和2.64倍(有剂量校正);缓释剂型组的C0与AUC0~24h的相关性良好。结论:他克莫司普通剂型转换至缓释剂型时应该注意上调给药剂量,同时缓释剂型应结合CYP3A5的基因型检测,确保C0值在治疗窗范围内。

【Abstract】 Objective:To investigate the impact of CYP3A5 genetic polymorphism and modified release formulation on tacrolimus pharmacokinetics in Chinese stable renal transplant recipients.Method:Pharmacokinetics of once daily-tacrolimus(tac-q.d.) and twice daily-tacrolimus(tac-b.i.d.) were determined by CLIA,CYP3 A5 genotype was measured by PCR-RELP;Each 10 patients receiving tac-q.d.and tac-b.i.d.respectively were enrolled,and each 5 patients receiving tac-q.d.were matched to poor metabolism(PM) and fast metabolism(FM) group respectively according to CYP3 A5 genotypes.Result:AUC0~24 h for tac-q.d.was1.78 folds higher than AUC0~12 h for tac-b.i.d.,and dose-adjusted Co was 40% lower for tac-q.d.than for tac-b.i.d.There were no significant differences for other parameters between the two group;Cmax,AUC0~24 h and C0 were 1.75,1.96 and 2.49 folds higher for PM than for FM,and dose-adjusted Cmax,AUC0~24 h and C0 were1.80,2.34 and 2.64 folds higher for PM than for FM;There were good correlation between AUC0~24 h and Co for tac-b.i.d..Conclusion:Conversion from tac-q.d.to tac-b.i.d.results in requirement of increased tacrolimus dose and detection of CYP3 A5 genotype,which is necessary to ensure Co in the range of therapeutic window.

  • 【会议录名称】 第五届全国治疗药物监测学术年会论文汇编
  • 【会议名称】第五届全国治疗药物监测学术年会
  • 【会议时间】2015-09-17
  • 【会议地点】中国北京
  • 【分类号】R699.2;R969
  • 【主办单位】中国药理学会治疗药物监测研究专业委员会、中日友好医院
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