No pharmacokinetic interactions between mycophenolic acid and tacrolimus in renal transplant recipients
No pharmacokinetic interactions between mycophenolic acid and tacrolimus in renal transplant recipients
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DOI：
10.1111/j.1365-2710.2008.00906.x
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发表时间：
2008-04-01
影响因子：
2
通讯作者：
Suzuki, T.
中科院分区：
文献类型：
--
作者：
Kagaya, H.;Miura, M.;Suzuki, T.
目的：研究71例日本肾移植受者中霉酚酸（MPA）、霉酚酸酯（MMF）的活性代谢物与他克莫司之间的药物相互作用，以及CYP3A5和UGT2B7基因多态性对这些药物相互作用的影响。方法：接受他克莫司与MMF联合免疫抑制治疗。移植后第28天，分别用高效液相色谱法和微粒酶免疫分析法测定MPA和他克莫司的浓度。结果：在观察到的血浆浓度-时间曲线（AUC(0-12)）下的总面积MPA < 70 mu g.h/mL的接受者中，急性排斥反应的发生率是AUC（0-12）值较高的接受者的两倍多（17%比7%）。使用该截止AUC值，急性排斥反应（AR）的敏感性为70.6%，特异性为55.6%。他克莫司的AUC（0-12）、最大血药浓度、谷血药浓度或口服清除率均不随MPA剂量或AUC的变化而变化。他克莫司C-0 3组间MPA药代动力学参数也无显著差异
Objective: The aim of this study was to investigate drug interactions between mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF) and tacrolimus, as well as the impact of CYP3A5 and UGT2B7 genetic polymorphisms on these drug interactions in 71 Japanese renal transplant recipients.Methods: Recipients received combination immunosuppressive therapy consisting of tacrolimus and MMF. On day 28 after transplantation, the concentrations of MPA and tacrolimus were measured by high-performance liquid chromatography and microparticle enzyme immunoassay respectively.Results: Acute rejection was over twice more common in recipients with a total area under the observed plasma concentration-time curve (AUC(0-12)) of MPA < 70 mu g.h/mL than in those with higher values AUC(0-12) values (17% vs. 7%).Using this cut-off AUC value, sensitivity was 70.6% and specificity 55.6% for acute rejection (AR). There was no change in AUC(0-12), maximum plasma concentration, trough plasma concentration, or oral clearance of tacrolimus with variation in dosage or AUC of MPA. There were also no significant differences in the MPA pharmacokinetic parameters among three tacrolimus C-0 groups: 5