Taylor W B, Simpson J M, Bateman D N
Wolfson Unit of Clinical Pharmacology, University of Newcastle upon Tyne, UK.
Eur J Clin Pharmacol. 1987;33(2):161-5. doi: 10.1007/BF00544561.
We have carried out a randomized, double-blind trial to investigate the relationship between the dose and plasma concentration of metoclopramide and its anti-emetic efficacy and adverse effects in patients receiving cancer chemotherapy. Seventeen patients received four different infusion regimens of high-dose metoclopramide in random order with four consecutive courses of chemotherapy, to achieve an approximately eight-fold range in plasma metoclopramide concentrations. In patients receiving cisplatin the incidence of vomiting decreased with increasing metoclopramide dose, but the overall efficacy was poor. There was no relationship between anti-emetic efficacy and either dose or plasma concentration of metoclopramide in patients receiving cyclophosphamide and doxorubicin. The adverse effects of high-dose metoclopramide included diarrhoea, which increased in incidence with increasing metoclopramide dose, and sedation and extrapyramidal reactions, which were not related to dose or plasma concentration. Although anti-emetic efficacy increases with increasing metoclopramide dose in patients receiving cisplatin, high-dose metoclopramide alone does not adequately control cisplatin-induced nausea and vomiting.
我们开展了一项随机双盲试验，以研究接受癌症化疗的患者中，甲氧氯普胺的剂量与血药浓度之间的关系，及其止吐疗效和不良反应。17名患者在连续四个疗程的化疗中，随机接受了四种不同的高剂量甲氧氯普胺输注方案，以使血浆中甲氧氯普胺浓度达到约八倍的范围。在接受顺铂治疗的患者中，呕吐发生率随甲氧氯普胺剂量增加而降低，但总体疗效较差。在接受环磷酰胺和阿霉素治疗的患者中，止吐疗效与甲氧氯普胺的剂量或血药浓度均无关联。高剂量甲氧氯普胺的不良反应包括腹泻，其发生率随甲氧氯普胺剂量增加而升高，以及镇静和锥体外系反应，这两者与剂量或血药浓度无关。尽管在接受顺铂治疗的患者中，止吐疗效随甲氧氯普胺剂量增加而提高，但单独使用高剂量甲氧氯普胺并不能充分控制顺铂引起的恶心和呕吐。
