Budde Klemens, Glander Petra, Krämer Bernhard K, Fischer Wolfgang, Hoffmann Ute, Bauer Steffen, Grohmann Jana, Neumayer Hans-Hellmut, Arns Wolfgang
Department of Nephrology, University Hospital Charité, Berlin, Germany.
Transplantation. 2007 Feb 27;83(4):417-24. doi: 10.1097/01.tp.0000251969.72691.ea.
Mycophenolic acid (MPA) pharmacokinetics using the mycophenolate mofetil (MMF) formulation are known to differ between patients receiving tacrolimus or cyclosporine, but only limited data exist concerning concomitant use of tacrolimus and enteric-coated mycophenolate sodium (EC-MPS).
In this six-month, multicenter, open-label, single-arm trial, 63 maintenance renal transplant patients receiving tacrolimus were converted from mycophenolate mofetil (MMF) to EC-MPS.
MPA concentration-time profiles in 21 patients showed that MPA exposure was similar with MMF or EC-MPS (mean area under the curve 39.9+/-11.6 microg x h/mL versus 43.7+/-17.4 microg x h/mL at day 14 post-conversion). Median time to peak concentration was 0.5 hr with MMF and 1.5 hr with EC-MPS. Inosine monophosphate dehydrogenase (IMPDH) activity was almost identical: area under the enzyme activity time curve (AEC) was 124.2+/-32.0 nmol x h/mg prot/h with MMF and 130.3+/-36.6 nmol x h/mg prot/h with EC-MPS at 14 days post-conversion; average daytime IMPDH activity was 10.3+/-2.7 nmol/h/mg protein and 10.9+/-2.7 nmol/h/mg protein, respectively. Maximal daytime inhibition of IMPDH activity was 67% with MMF and 62% with EC-MPS at day 14. One patient (1.6%) experienced mild biopsy-proven acute rejection. No graft losses or deaths occurred. Renal function remained stable (mean calculated creatinine clearance 70.6+/-26.8 mL/min with MMF and 68.8+/-25.4 mL/min six months post-conversion). Adverse events or infections with a suspected relation to EC-MPS occurred in 12 patients (19%). Four patients discontinued EC-MPS due to adverse events or infections.
MMF and EC-MPS are associated with similar MPA exposure and equivalent pharmacodynamic effect. Conversion of tacrolimus-treated maintenance renal transplant patients from MMF to EC-MPS is safe and well-tolerated and does not compromise therapeutic efficacy.
已知使用霉酚酸酯（MMF）制剂时，霉酚酸（MPA）的药代动力学在接受他克莫司或环孢素的患者之间存在差异，但关于他克莫司与肠溶衣霉酚酸钠（EC-MPS）联合使用的数据有限。
在这项为期6个月的多中心、开放标签、单臂试验中，63例接受他克莫司治疗的维持性肾移植患者从霉酚酸酯（MMF）转换为EC-MPS。
21例患者的MPA浓度-时间曲线表明，转换后第14天，MMF和EC-MPS的MPA暴露量相似（曲线下平均面积分别为39.9±11.6μg·h/mL和43.7±17.4μg·h/mL）。MMF的达峰时间中位数为0.5小时，EC-MPS为1.5小时。肌苷单磷酸脱氢酶（IMPDH）活性几乎相同：转换后14天，MMF组酶活性时间曲线下面积（AEC）为124.2±32.0nmol·h/mg蛋白/h，EC-MPS组为130.3±36.6nmol·h/mg蛋白/h；白天平均IMPDH活性分别为10.3±2.7nmol/h/mg蛋白和10.9±2.7nmol/h/mg蛋白。转换后第14天，MMF和EC-MPS对IMPDH活性的最大白天抑制率分别为67%和62%。1例患者（1.6%）经活检证实发生轻度急性排斥反应。未发生移植肾丢失或死亡。肾功能保持稳定（转换后6个月，MMF组平均计算肌酐清除率为70.6±26.8mL/min，EC-MPS组为68.8±25.4mL/min）。12例患者（19%）发生了与EC-MPS疑似相关的不良事件或感染。4例患者因不良事件或感染停用EC-MPS。
MMF和EC-MPS的MPA暴露量相似，药效学效应相当。将接受他克莫司治疗的维持性肾移植患者从MMF转换为EC-MPS是安全且耐受性良好的，不影响治疗效果。
