霉酚酸酯不良反应与血药浓度的关系

Impact of MPA Pharmacokinetics on MMF-Related Side Effects

目的探讨我国肾移植受者霉酚酸酯(MMF)不良反应与血浆总霉酚酸(MPA)浓度之间的关系。方法对2003年6月~2004年1月期间21例首次同种异体尸体肾移植受者进行MPA浓度检测,应用HPLC方法测定5个拟定时间点血浆总MPA浓度(C0、C30、C1、C2、C4),共105例次,公式计算MPA-AUC0-12h。根据肾移植术后早期是否出现MMF相关的不良反应进行分组,分析两组间MPA浓度以及MPA-AUC0~12h的差异。结果不良反应组MPA-AUC0~12h高于无不良反应组,分别为(61.67±26.82)mg.h.L-1和(48.41±15.54)mg.h.L-1,但无统计学差异(P>0.05);不良反应组C30(17.18±7.37)mg/L远高于无不良反应组(8.72±6.05)mg/L(P<0.05)。结论肾移植术后早期MMF相关的不良反应以胃肠道为主,其发生率与C30密切相关;肾移植术后早期临床监测血浆总MPA浓度有益于MMF的个体化应用。

ObjectiveTo investigate the impact of mycophenolic acid(MPA) pharmacokinetics on its side effects.(Methods)MPA plasma concentration profiles were measured by HPLC. Twenty-one recipients received renal transplantation between June 2003 and January 2004.The number of limited sampling (C_(0), C_(30), C_(1), C_(2), C_(4)) was 105 totally. All recipients were divided into 2 groups: side effects group (S-group, n=8), and non-side effects group (N-group, n=13).ResultsMPA-AUC_(0~12h) in S-group(61.6726.82) mghL^(-1)was higher than that in N-group(48.4115.54) mghL^(-1 ), but not statistically significant(P>0.05). However, C_(30) in S-group (17.18(7.37)) mg/L was significantly higher than that in N-group(8.726.05)mg/L(P<0.05).Conclusion(There is a) favorable correlation between C_(30) and side effects.Gastrointestinal toxicity is the dominant side effect of (orally) administered MMF during early stage after renal transplantation. It is necessary to perform clinical therapeutic drug monitoring of MPA after renal transplantation.