McDermed J E, Cohen J L, Joseph C, Strum S B
J Clin Oncol. 1985 Oct;3(10):1400-8. doi: 10.1200/JCO.1985.3.10.1400.
Using a sensitive and specific high-pressure liquid chromatographic (HPLC) assay, we measured serum levels of metoclopramide in 18 cancer patients receiving high-dose intravenous (IV) therapy to prevent cisplatin-induced emesis. Ten patients were treated with one or more courses with metoclopramide alone (1.0 to 3.0 mg/kg) in an open-label study, and eight patients were treated with a fixed 2.0 mg/kg dose of metoclopramide with or without adjunct dexamethasone (20 mg) using a randomized, crossover design. The pharmacokinetics of metoclopramide were determined, and the relationship between serum levels and clinical response was evaluated. The pharmacokinetic parameters of high-dose metoclopramide were found to be similar to those reported for standard promotility doses, and no dose dependency was demonstrated over the range of doses studied. No clear correlation between serum metoclopramide levels and prevention of cisplatin-induced emesis was observed. The addition of dexamethasone resulted in clinical improvement in two of eight patients, but had no effect on serum metoclopramide levels or kinetic parameters. Results in this study population do not show metoclopramide levels to be related to antiemetic effect following IV cisplatin therapy.
我们采用灵敏且特异的高压液相色谱（HPLC）分析法，测定了18例接受大剂量静脉注射（IV）治疗以预防顺铂所致呕吐的癌症患者的血清胃复安水平。在一项开放标签研究中，10例患者单独接受一个或多个疗程的胃复安治疗（1.0至3.0mg/kg），8例患者采用随机交叉设计，接受固定剂量2.0mg/kg的胃复安治疗，同时或不同时联用辅助地塞米松（20mg）。测定了胃复安的药代动力学，并评估了血清水平与临床反应之间的关系。发现大剂量胃复安的药代动力学参数与标准促动力剂量所报告的参数相似，在所研究的剂量范围内未显示出剂量依赖性。未观察到血清胃复安水平与预防顺铂所致呕吐之间存在明显相关性。联用的地塞米松使8例患者中的2例临床症状改善，但对血清胃复安水平或动力学参数无影响。该研究人群的结果未显示胃复安水平与顺铂静脉治疗后的止吐效果相关。
