van Hest Reinier M, Doorduijn Jeanette K, de Winter Brenda C M, Cornelissen Jan J, Vulto Arnold G, Oellerich Michael, Löwenberg Bob, Mathot Ron A A, Armstrong Victor William, van Gelder Teun
Department of Hospital Pharmacy (Clinical Pharmacology Unit), Erasmus MC, Rotterdam, The Netherlands.
Ther Drug Monit. 2007 Jun;29(3):353-60. doi: 10.1097/FTD.0b013e31805d8816.
Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is increasingly used in the prophylaxis of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HCT). Few pharmacokinetic data are available about the use of MMF for this indication. This case series aimed at analyzing the pharmacokinetics of MMF in a population of HCT recipients representative for everyday practice. From 15 HCT recipients, serial plasma samples were taken after twice-daily oral intake of MMF. Plasma concentrations of total MPA and its glucuronide metabolites, as well as free MPA, were quantified. Median apparent oral MPA clearance (CL/F), apparent half-life, and total MPA area under the curve for hours 0 to 12 (AUC0-12, normalized to 1000 mg MMF) were, respectively, 56 L/h (range: 29-98 L/h), 2.3 hours (range: 0.8-5.7 hours), and 18.0 mgh/L (range: 10-35 mgh/L). Total MPA concentrations were below 2 mg/L 8 hours after MMF administration, indicating reduced enterohepatic recirculation. Median free MPA AUC0-12 (normalized to 1000 mg MMF) was 224 microgh/L (range: 56-411 microgh/L). Because of high CL/F, total MPA exposure in HCT recipients is low and apparent half-life is short in comparison with reference values from renal transplantation. Exposure may be improved in HCT recipients by higher or more frequent MMF dosing.
霉酚酸酯（MMF）是霉酚酸（MPA）的前体药物，越来越多地用于造血干细胞移植（HCT）后移植物抗宿主病（GVHD）的预防。关于MMF用于该适应症的药代动力学数据很少。本病例系列旨在分析MMF在代表日常临床实践的HCT受者群体中的药代动力学。从15名HCT受者中，在每日两次口服MMF后采集系列血浆样本。对总MPA及其葡萄糖醛酸代谢物以及游离MPA的血浆浓度进行定量。口服MPA的中位表观清除率（CL/F）、表观半衰期以及0至12小时总MPA曲线下面积（AUC0-12，以1000mg MMF标准化）分别为56L/h（范围：29-98L/h）、2.3小时（范围：0.8-5.7小时）和18.0mg·h/L（范围：10-35mg·h/L）。MMF给药8小时后总MPA浓度低于2mg/L，表明肝肠循环减少。游离MPA的中位AUC0-12（以1000mg MMF标准化）为224μg·h/L（范围：56-411μg·h/L）。由于CL/F较高，与肾移植的参考值相比，HCT受者中总MPA暴露量较低且表观半衰期较短。通过更高剂量或更频繁地给予MMF，HCT受者的暴露量可能会得到改善。
