Taylor W B, Proctor S J, Bateman D N
Br J Clin Pharmacol. 1984 Nov;18(5):679-84. doi: 10.1111/j.1365-2125.1984.tb02529.x.
To avoid the accumulation of metoclopramide that occurs with repeated i.v. bolus doses, a new regimen for the administration of high-dose metoclopramide consisting of a loading dose followed by a continuous infusion was investigated to determine the pharmacokinetics and antiemetic efficacy of the drug when given in this manner. Nine patients with non-Hodgkin's lymphoma entered the study, of whom six completed the study, receiving each of three dosage schedules of metoclopramide during three consecutive courses of chemotherapy. In these six patients plasma metoclopramide half-life was 5.9 +/- 0.4 h (mean +/- s.e. mean) and plasma clearance was 25.4 +/- 4.8 l/h (mean +/- s.e. mean). Neither half-life nor clearance were dose-related. Steady-state was achieved during 9/18 infusions. Nausea and vomiting were completely controlled in 13/24 treatment courses (57%) and adverse effects were minimal. We conclude that steady-state plasma concentrations of metoclopramide can be achieved using a weight-related infusion regimen, though the optimum plasma concentration remains to be determined.
为避免重复静脉推注剂量时出现甲氧氯普胺蓄积，研究了一种高剂量甲氧氯普胺给药新方案，即先给予负荷剂量，随后持续输注，以确定以此方式给药时该药物的药代动力学和止吐疗效。9例非霍奇金淋巴瘤患者进入研究，其中6例完成研究，在连续3个化疗疗程中接受了3种甲氧氯普胺给药方案。在这6例患者中，血浆甲氧氯普胺半衰期为5.9±0.4小时（均值±标准误均值），血浆清除率为25.4±4.8升/小时（均值±标准误均值）。半衰期和清除率均与剂量无关。18次输注中有9次达到稳态。24个治疗疗程中有13个（57%）恶心和呕吐得到完全控制，且不良反应最小。我们得出结论，使用与体重相关的输注方案可实现甲氧氯普胺的稳态血浆浓度，尽管最佳血浆浓度仍有待确定。
