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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 evaluate the effect of pentasil on plasma concentrations of FK506 after renal transplantation in allogeneic patients and to observe the changes of cytochrome P4503A4 (CYP3A4) activity in vivo. Methods The patients after renal transplantation in our hospital were selected, 33 cases served as experimental group and 30 cases as control group. Patients were taken FK506 capsules for 4 weeks, then at different time points measured FK506 blood concentration, calculate the pharmacokinetic parameters, test various hematological indicators, and urine was collected to measure the CYP3A4 activity. Subsequent test group patients with pentacene tablets, the control group of patients is not the application of pentacene tablets; 21d again after the determination of the above items. Results Before and after the test, there was no significant difference in the pharmacokinetic parameters of FK506 in the control group (P> 0.05). In the test group, the changes of the pharmacokinetic parameters of FK506 after 21 days’ application of penta-ester tablets were: 31.06% increase in AUC0-12, 20.99% increase in ρmax, and 0.6 h delay in tmax, the difference was significant P <0.05). The activity of CYP3A4 was significantly decreased (P <0.05), but there was no significant difference between all the hematological parameters (P> 0.05). Conclusions The level of CYP3A4 activity is decreased after application of pentasodium ester tablets. The metabolism of FK506 is slowed down and the plasma concentration is increased. The area under the curve is increased, the peak concentration is increased and the peak concentration is prolonged.