Faculty of Pharmaceutical Sciences, University of British Columbia, Canada.
Ther Drug Monit. 2010 Jun;32(3):373-8. doi: 10.1097/FTD.0b013e3181d80c1b.
Given the paucity of data on pharmacokinetics of mycophenolic acid (MPA) in islet transplant, the aim of this study was to characterize pharmacokinetic parameters of MPA and its 2 glucuronidated metabolites in stable islet transplant recipients. Sixteen subjects were entered into this open-label study after written informed consent. Upon administration of a steady-state morning mycophenolate mofetil dose, 12-hour serial concentrations of MPA and its phenolic glucuronide (MPAG) and acyl-glucuronide (AcMPAG) were measured by a validated high-performance liquid chromatography method and pharmacokinetic parameters analyzed by noncompartmental modeling. Subjects included 11 women and 5 men who had received 2.7 +/- 0.8 islet transplants. Age was 50 +/- 8 years, weight 64 +/- 11 kg, serum albumin 4.2 +/- 0.3 g/dL, and serum creatinine 1.1 +/- 0.4 mg/dL. All patients were also on tacrolimus-based steroid-free immunosuppressant regimens. Mycophenolate mofetil dosage ranged from 1 to 2 g daily (25.4 +/- 6.1 mg/kg/d). Pharmacokinetic parameters for MPA were area under the curve 42.9 +/- 21.6 microg h/mL; dose-normalized AUC 52.9 +/- 25.4 microg h/mL/g; maximal concentration (Cmax) 13.0 +/- 6.2 microg/mL; time to Cmax (tmax) 1.2 +/- 0.4 hours; minimum concentration (Cmin) 1.4 +/- 1.0 microg/mL; and MPA-free fraction 1.2% +/- 1.0%. Area under the curve ratios of MPAG/MPA and AcMPAG/MPA were 17.8 +/- 12.4 and 0.1 +/- 0.1, respectively. The wide interpatient variability in all pharmacokinetic parameters of MPA and metabolites are consistent with results from the only other published pharmacokinetic study in islet transplant recipients. A population model and a search for significant covariates may help reduce this variability. Pharmacokinetic parameters calculated in the present study, coupled with findings from the only other published MPA study in islet transplant, form a preliminary base on which to build a population model for future multicenter studies of this little-studied transplant subpopulation.
由于在胰岛移植中有关霉酚酸（MPA）药代动力学的数据很少，本研究的目的是描述稳定胰岛移植受者中 MPA 及其 2 种葡萄糖醛酸化代谢物的药代动力学参数。在书面知情同意后，16 名受试者进入了这项开放标签研究。在给予稳态早晨霉酚酸酯剂量后，通过验证的高效液相色谱法测量了 12 小时连续 MPA 及其酚基葡萄糖醛酸（MPAG）和酰基葡萄糖醛酸（AcMPAG）浓度，并通过非房室模型分析了药代动力学参数。受试者包括 11 名女性和 5 名男性，他们接受了 2.7 ± 0.8 胰岛移植。年龄为 50 ± 8 岁，体重 64 ± 11 公斤，血清白蛋白 4.2 ± 0.3 g/dL，血清肌酐 1.1 ± 0.4 mg/dL。所有患者还接受了基于他克莫司的无类固醇免疫抑制剂方案。霉酚酸酯剂量范围为 1 至 2 克/天（25.4 ± 6.1 mg/kg/d）。MPA 的药代动力学参数为曲线下面积 42.9 ± 21.6 µg h/mL；剂量标准化 AUC 52.9 ± 25.4 µg h/mL/g；最大浓度（Cmax）13.0 ± 6.2 µg/mL；达峰时间（tmax）1.2 ± 0.4 小时；最小浓度（Cmin）1.4 ± 1.0 µg/mL；MPA 游离分数 1.2% ± 1.0%。MPAG/MPA 和 AcMPAG/MPA 的 AUC 比值分别为 17.8 ± 12.4 和 0.1 ± 0.1。MPA 和代谢物所有药代动力学参数的患者间变异性均较大，与唯一另一项发表的胰岛移植受者药代动力学研究结果一致。群体模型和对显著协变量的搜索可能有助于减少这种变异性。本研究中计算的药代动力学参数，加上唯一另一项发表的 MPA 在胰岛移植中的研究结果，为未来对这一研究较少的移植亚群进行多中心研究建立了一个初步的基础。
