de Winter Brenda C M, Mathôt Ron A A, van Hest Reinier M, van Gelder Teun
Erasmus Medical Center, Department of Hospital Pharmacy, Clinical Pharmacology Unit, Rotterdam, The Netherlands.
Expert Opin Drug Metab Toxicol. 2007 Apr;3(2):251-61. doi: 10.1517/17425255.3.2.251.
Treatment with the immunosuppressive agent mycophenolate mofetil (MMF) decreases the risk of rejection after renal transplantation and improves graft survival compared with azathioprine. The exposure to the active metabolite mycophenolic acid (MPA) is correlated to the risk of developing acute rejection. The interpatient variability in exposure of MPA is wide relative to the proposed therapeutic window of the MPA AUC(0 12) (30 - 60 mg.h/l). The pharmacokinetics of MPA are influenced by patient characteristics such as gender, time after transplantation, serum albumin concentration, renal function, comedication and pharmacogenetic factors. Therapeutic drug monitoring is likely to reduce inter-patient variability. Limited sampling strategies are used to predict the full AUC(0 12). Three prospective randomised studies compared concentration controlled MMF therapy to a fixed-dose regimen. Preliminary outcomes of these studies showed conflicting results and longer follow up is needed to further clarify the role of therapeutic drug monitoring in increasing the therapeutic potential of MMF.
与硫唑嘌呤相比，使用免疫抑制剂霉酚酸酯（MMF）进行治疗可降低肾移植后排异反应的风险，并提高移植肾的存活率。活性代谢产物霉酚酸（MPA）的暴露量与发生急性排异反应的风险相关。相对于MPA曲线下面积（AUC）（0至12）所建议的治疗窗（30 - 60 mg·h/l），患者间MPA暴露量的变异性较大。MPA的药代动力学受患者特征影响，如性别、移植后时间、血清白蛋白浓度、肾功能、合并用药及药物遗传学因素等。治疗药物监测可能会减少患者间的变异性。有限采样策略用于预测完整的AUC（0至12）。三项前瞻性随机研究将浓度控制的MMF治疗与固定剂量方案进行了比较。这些研究的初步结果显示出相互矛盾的结果，需要更长时间的随访来进一步阐明治疗药物监测在提高MMF治疗潜力方面的作用。
