肾移植术后不同时间麦考酚酸暴露量的变化——附16例报告

Changes in mycophenolic acid exposure at different posttransplant time in kidney transplant recipients

目的:观察肾移植术后不同时间麦考酚酸暴露量的变化,为肾移植术后麦考酚吗乙酯剂量的调整提供理论依据。方法:16例首次肾移植患者,均于肾移植术后24小时内给予麦考酚吗乙酯(mycophenolate mofetil,MMF)1.5g/d治疗,长期应用。于术后第7日、第28日、第90日测定其服药前、服药后半小时及服药后2小时的麦考酚酸的血药浓度,采用Shaw简易公式计算对应的麦考酚酸血药浓度-时间曲线下面积(the area under the drug concentration in the plasma versurs time curve,AUC)并比较其差异。结果:术后第7日、第28日、第90日的麦考酚酸AUC分别为(32±9)(mg/L).h、(41±10)(mg/L).h和(47±13)(mg/L).h,比较差异均有统计学意义(均为P<0.05)。结论:在术后3个月内连续服用同等剂量(1.5g/d)MMF的情况下,麦考酚酸AUC逐渐升高,在术后第90日达到(47±13)(mg/L).h,已超过能有效预防急性排斥反应的AUC。提示应在用药的90日内监测麦考酚酸AUC,并及时减少用量,以免发生严重的不良反应。

Objective： To investigate the changes of mycophenolic acid （MPA） exposure in kidney transplant recipients at different posttransplant time, in order to provide a theoretical basis for dose modification of MMF. Methods. Sixteen patients who received kidney transplant firstly were enrolled, MMF 1.5 g/d was administered within 24 hours after transplantion and thereafter. On the 7^th, 280, and 90^th posttransplant day, plasma MPA concentrations ofO （predose） , 0. 5 and 2 hours after the morning dose of MMF were measured, and MPA AUC was calculated by using Shaw＇s equation. Results： MPA AUC of the 7^th, 28^th and 90^th posttransplant day was （32±9） （mg/L） · h, （41 ± 10） （mg/L） · h and （47 ± 13） （mg/L） · h respectively, with a significant difference between every two groups （P 〈0. 05）. Conclusion： MPA AUC increases with time when the dose remained unchanged （1.5 g/d） in 3 post-operation months and reaches up to （47 ±13） （mg/L） · h at 90^th posttransplant day, which exceeds the AUC for effective prevention of acute rejection, suggesting that MPA AUC within 90 posttransplant days should be monitored and the dose of MMF should be reduced in order to avoid severe adverse events.