Rupprecht Korbinian, Schmidt Christoph, Raspé Anne, Schweda Frank, Shipkova Maria, Fischer Wolfgang, Bucher Michael, Kees Frieder, Faerber Lothar
Department of Anesthesiology, University of Regensburg, Regensburg, Germany.
J Clin Pharmacol. 2009 Oct;49(10):1196-201. doi: 10.1177/0091270009344988.
The influence of pantoprazole 40 mg twice daily on the bioavailability of a single dose of mycophenolate mofetil 1000 mg or enteric-coated mycophenolate sodium is investigated in healthy volunteers. The plasma concentrations of mycophenolic acid and of the inactive metabolite mycophenolic acid glucuronide are measured by high-performance liquid chromatography. The pharmacokinetic parameters following sole administration are similar for mycophenolate mofetil and enteric-coated mycophenolate sodium except for the time to peak concentration, which is longer in the enteric-coated mycophenolate sodium group. Concomitant treatment with pantoprazole significantly (P < .001) lowers the mycophenolic acid exposure following administration of mycophenolate mofetil. The peak concentrations drop by 57%, and area under the curve decreases from 0 to 12 hours by 27%. In contrast, pantoprazole does not change the pharmacokinetics of enteric-coated mycophenolate sodium. Given that mycophenolic acid exposure correlates with the incidence of biopsy-proven acute rejections in renal transplant recipients, these findings may have clinical implications. Administration of pantoprazole in combination with mycophenolate mofetil could possibly result in an insufficient mycophenolic acid exposure, increasing the risk of treatment failure.
在健康志愿者中研究了每日两次服用40毫克泮托拉唑对单次服用1000毫克吗替麦考酚酯或肠溶包衣吗替麦考酚钠生物利用度的影响。通过高效液相色谱法测定霉酚酸及其无活性代谢产物霉酚酸葡糖苷酸的血浆浓度。除达峰时间外，单独给药后吗替麦考酚酯和肠溶包衣吗替麦考酚钠的药代动力学参数相似，肠溶包衣吗替麦考酚钠组的达峰时间更长。泮托拉唑联合用药显著（P <.001）降低了吗替麦考酚酯给药后霉酚酸的暴露量。峰浓度下降57%，0至12小时的曲线下面积减少27%。相比之下，泮托拉唑不会改变肠溶包衣吗替麦考酚钠的药代动力学。鉴于霉酚酸暴露与肾移植受者经活检证实的急性排斥反应发生率相关，这些发现可能具有临床意义。泮托拉唑与吗替麦考酚酯联合使用可能会导致霉酚酸暴露不足，增加治疗失败的风险。
