五酯片对同种异体肾移植术后普乐可复血药浓度影响的观察  

Effect of Wuzhi Tablets on the Prograf Concentration After Allograft Renal Transplantation

作　　者：翁国斌 高文波 任雨 唐莉 

机构地区：[1]宁波市泌尿肾病医院肾移植科,浙江宁波315100

出　　处：《中国药学杂志》2009年第11期857-860,共4页Chinese Pharmaceutical Journal

摘　　要：目的评价同种异体肾移植术后患者应用五酯片对普乐可复(FK506)血药浓度的影响,并观察其体内细胞色素P4503A4酶(CYP3A4)活性的变化情况。方法选取我院肾移植术后患者,33例作为试验组,30例作为对照组。患者均服用FK506胶囊4周,随后在不同时间点测定FK506血药浓度,计算其药动学参数,检测各项血液学指标,并留取尿液,测定其CYP3A4活性。随后试验组患者加用五酯片,对照组患者则不应用五酯片;21d后再次测定上述项目。结果试验前后,对照组患者FK506各项药动学参数的差异没有显著性(P>0.05)。试验组患者应用五酯片21d后,其FK506药动学参数的变化情况为:AUC0～12大约增加了31.06%,ρmax大约增加了20.99%,tmax延迟约0.6h,其差异均有显著性(P<0.05),CYP3A4的活性显著下降(P<0.05),而各项血液学检测指标之间没有差异性(P>0.05)。结论应用五酯片后,患者CYP3A4活性水平下降,使FK506的代谢减慢、血药浓度升高,导致其曲线下面积增大、峰浓度升高,达峰浓度的时间延长。OBJECTIVE To assess the influence of Wuzhi tablets on the prograf concentration after allograft renal transplantation, and to observe the activities of CYP3A4. METHODS After renal transplantation, thirty-three patients were enrolled into experiment group and thirty patients into control group. All of them took FK506 as part of immunosuppression for four weeks, then the FK506 concentrations at different time points were measured. Pharmacokinetic parameters and hematological parameters were estimated. The CYP3A4 activities were measured. Thereafter, the patients in experiment group were administered with Wuzhi tablets. Twenty-one days later, the same items were recorded again. RESULTS In control group, there was no statistical difference in their kinetic parameters of FK506 before and after the experiment （P〉0.05）. In experiment group, after 21 d of administration of Wuzhi tablets, the pharmacokinetic parameters of FK506 changed significantly （P〈0.05）. AUC0-12 was increased by about 31.06%. Pmax was increased by about 20.99%. tmax was delayed about 0.6 h, and the activities of CYP3A4 was decreased significantly （P〈0.05）. There was no significant difference between hematological parameters （P〉0.05）. CONCLUSION Wuzhi tablets could inhibit the activity of CYP3A4 and increase the FK506 concentrations, leading to the increase of the area under curve and peak concentration of the drug, and delaying the time to peak concentration.

关 键 词：同种异体肾移植 五酯片 普乐可复 血药浓度 

分 类 号：R969.1[医药卫生—药理学]