Wadhwa N K, Schroeder T J, O'Flaherty E, Pesce A J, Myre S A, First M R
Transplantation. 1987 Feb;43(2):211-3. doi: 10.1097/00007890-198702000-00009.
This study was performed to determine the effect of coadministered oral metoclopramide on the absorption of oral cyclosporine in 14 kidney transplant patients. The study was conducted on two consecutive days. Ten patients were studied twice, and 4 patients once, giving 24 studies. The total dosage of metoclopramide was 20 mg. The day on which metoclopramide was administered was chosen randomly. Whole-blood cyclosporine levels were analyzed by high-performance liquid chromatography. Coadministration of cyclosporine with metoclopramide resulted in a significant increase in mean maximum blood concentration (567 ng/ml versus 388 ng/ml) and mean area under the blood-concentration-versus-time curve (4120 ng X hr/ml versus 3370 ng X hr/ml); and a significant decrease in mean time to reach maximum concentration. The mean increase in area under the blood-concentration-versus-time curve was 29%. No significant changes were observed in the elimination of cyclosporine when it was coadministered with metoclopramide. These observations suggest that coadministered metoclopramide increased the total absorption of cyclosporine. Metoclopramide has been shown to hasten gastric emptying; since cyclosporine is absorbed predominantly in the small intestine, coadministration of metoclopramide resulted in increased bioavailability of cyclosporine.
本研究旨在确定在14例肾移植患者中，联合使用口服甲氧氯普胺对口服环孢素吸收的影响。研究在连续两天进行。10例患者进行了两次研究，4例患者进行了一次研究，共进行了24项研究。甲氧氯普胺的总剂量为20mg。给药甲氧氯普胺的日期随机选择。全血中环孢素水平通过高效液相色谱法分析。环孢素与甲氧氯普胺联合给药导致平均最大血药浓度显著升高（分别为567ng/ml和388ng/ml），血药浓度-时间曲线下平均面积显著增加（分别为4120ng·hr/ml和3370ng·hr/ml）；达到最大浓度的平均时间显著缩短。血药浓度-时间曲线下面积的平均增加为29%。环孢素与甲氧氯普胺联合给药时，其消除过程未观察到显著变化。这些观察结果表明，联合使用甲氧氯普胺增加了环孢素的总吸收量。甲氧氯普胺已被证明可加速胃排空；由于环孢素主要在小肠吸收，联合使用甲氧氯普胺导致环孢素的生物利用度增加。
