van Hest Reinier M, Hesselink Dennis A, Vulto Arnold G, Mathot Ron A A, van Gelder Teun
Department of Hospital Pharmacy, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Expert Opin Pharmacother. 2006 Mar;7(4):361-76. doi: 10.1517/14656566.7.4.361.
The immunosuppressive agent mycophenolate mofetil has been successfully used over the past 10 years to prevent acute allograft rejection after renal transplantation. It has mainly been administered as a fixed dose of mycophenolate mofetil 1000 mg b.i.d. The pharmacokinetics of mycophenolic acid, the active moiety of the prodrug mycophenolate mofetil, show large between-patient variability, and exposure to mycophenolic acid correlates with the risk for acute rejection. This suggests that already excellent clinical results can be further improved by mycophenolate mofetil dose individualization. This review discusses different arguments in favour of individualization of mycophenolate mofetil dose, as well as strategies for managing mycophenolate mofetil therapy individualization, including pharmacokinetic and pharmacodynamic monitoring and dose individualization based on pharmacogenetic information. It is expected that pharmacokinetic monitoring of mycophenolic acid will offer the most effective and feasible tool for mycophenolate mofetil dose individualization.
免疫抑制剂霉酚酸酯在过去10年中已成功用于预防肾移植后的急性移植物排斥反应。它主要以固定剂量的霉酚酸酯1000毫克每日两次给药。前药霉酚酸酯的活性部分霉酚酸的药代动力学显示患者间差异很大,且霉酚酸的暴露量与急性排斥反应风险相关。这表明,通过霉酚酸酯剂量个体化,已有的出色临床结果可以进一步改善。本综述讨论了支持霉酚酸酯剂量个体化的不同论据,以及管理霉酚酸酯治疗个体化的策略,包括药代动力学和药效学监测以及基于药物遗传学信息的剂量个体化。预计霉酚酸的药代动力学监测将为霉酚酸酯剂量个体化提供最有效且可行的工具。