Czock David, Rasche Franz Maximilian, Carius Alexander, Glander Petra, Budde Klemens, Bauer Steffen, Keller Frieder, von Müller Lutz
University Hospital Ulm, Medical Department I, Division of Nephrology, Robert-Koch-Str. 8, 89070 Ulm, Germany.
J Clin Pharmacol. 2007 Jul;47(7):850-9. doi: 10.1177/0091270007301624. Epub 2007 May 25.
Mycophenolic acid can be administered orally using mycophenolate mofetil or enteric-coated mycophenolate. In renal transplant patients on immunosuppressant combination therapy, the overall mycophenolic acid exposure after oral dosing with mycophenolate mofetil and enteric-coated mycophenolate is similar. This study compared pharmacokinetics and pharmacodynamics of mycophenolic acid after equivalent doses of enteric-coated mycophenolate (360 mg twice daily) or mycophenolate mofetil (500 mg twice daily) in 7 patients with progressive IgA nephritis (glomerular filtration rate 20-35 mL/min) using a randomized crossover design. The pharmacokinetics of mycophenolic acid concentrations and pharmacodynamics (using inosine 5'-monophosphate dehydrogenase activity as a bio-marker) were sequentially monitored for 12 hours. After enteric-coated mycophenolate treatment, the mycophenolic acid peak concentration (Cmax = 12.8 vs 6.0 microg/mL, P < .05) and the overall exposure were significantly higher (AUC = 60.9 vs 40.7 microg.h/mL, P < .05), and the apparent clearance was significantly lower (CL/F = 7.9 vs 10.7 L/h, P < .05) as compared to that after mycophenolate mofetil. Paradoxically, inosine 5'-monophosphate dehydrogenase activity was not significantly different. In conclusion, the steady-state mycophenolic acid exposure was higher during treatment with enteric-coated mycophenolate as compared to mycophenolate mofetil, which might be explained by more extensive enterohepatic recycling of mycophenolic acid after administration of enteric-coated mycophenolate, whereas inosine 5'-monophosphate dehydrogenase suppression was not different.
霉酚酸可通过口服霉酚酸酯或肠溶衣霉酚酸来给药。在接受免疫抑制剂联合治疗的肾移植患者中，口服霉酚酸酯和肠溶衣霉酚酸后霉酚酸的总体暴露量相似。本研究采用随机交叉设计，比较了7例进行性IgA肾病（肾小球滤过率20 - 35 mL/min）患者在等效剂量的肠溶衣霉酚酸（每日两次，每次360 mg）或霉酚酸酯（每日两次，每次500 mg）治疗后霉酚酸的药代动力学和药效学。连续12小时监测霉酚酸浓度的药代动力学和药效学（以肌苷5'-单磷酸脱氢酶活性作为生物标志物）。与霉酚酸酯治疗后相比，肠溶衣霉酚酸治疗后霉酚酸的峰值浓度（Cmax = 12.8 vs 6.0 μg/mL，P <.05）和总体暴露量显著更高（AUC = 60.9 vs 40.7 μg·h/mL，P <.05），表观清除率显著更低（CL/F = 7.9 vs 10.7 L/h，P <.05）。矛盾的是，肌苷5'-单磷酸脱氢酶活性并无显著差异。总之，与霉酚酸酯相比，肠溶衣霉酚酸治疗期间霉酚酸的稳态暴露量更高，这可能是由于服用肠溶衣霉酚酸后霉酚酸的肠肝循环更广泛，而肌苷5'-单磷酸脱氢酶的抑制作用并无差异。
