Fetting J H, McCarthy L E, Borison H L, Colvin M
Cancer Treat Rep. 1982 Aug;66(8):1625-9.
Cyclophosphamide and phosphoramide mustard produce significant vomiting. Cyclophosphamide is metabolized to phosphoramide mustard, which may ultimately contribute to vomiting after cyclophosphamide administration. The role of the chemoreceptor trigger zone (CTZ) in vomiting caused by these agents is unknown. We studied the emetic syndromes produced by iv and intracerebroventricular cyclophosphamide and phosphoramide mustard in unanesthetized normal and CTZ-ablated cats. Iv cyclophosphamide produced vomiting unpredictably, with a mean latency of 54 +/- 9 mins (mean +/- SE) in cats that vomited. A dose-response relationship was found for phosphoramide mustard-induced emesis. A dose of 200 mg/kg was consistently effective, with a mean latency of 127 +/- 6 mins. Neither agent produced predictable emesis by the intracerebroventricular route of administration. One of four CTZ-ablated cats vomited after 300 mg/kg of cyclophosphamide. Since cyclophosphamide was an unpredictable emetic stimulus, it was not possible to further evaluate the effect of CTZ ablation on cyclophosphamide-induced vomiting. However, CTZ-ablated cats given 200 mg/kg of phosphoramide mustard vomited significantly less frequently (P = 0.05 by chi-square test) and with a longer latency than nonablated animals. A temporary, severe neurotoxic reaction was observed in cats receiving greater than or equal to 3400 mg/kg of cyclophosphamide, which may have had an inhibitory effect on emesis. Phosphoramide mustard was found to be a potent emetic stimulus in cats and may contribute to the emetic response following cyclophosphamide administration. Analysis of latency data suggests that in the cat other cyclophosphamide metabolites may also contribute to the emetic syndrome.
环磷酰胺和磷酰胺氮芥会引起严重呕吐。环磷酰胺会代谢为磷酰胺氮芥，这可能是环磷酰胺给药后引发呕吐的最终原因。化学感受器触发区（CTZ）在这些药物所致呕吐中的作用尚不清楚。我们研究了静脉注射和脑室内注射环磷酰胺及磷酰胺氮芥在未麻醉的正常猫和CTZ切除猫中产生的呕吐综合征。静脉注射环磷酰胺引发呕吐的情况不可预测，呕吐的猫平均潜伏期为54±9分钟（平均值±标准误）。发现磷酰胺氮芥诱导呕吐存在剂量反应关系。200mg/kg的剂量始终有效，平均潜伏期为127±6分钟。两种药物通过脑室内给药途径均未产生可预测的呕吐。四只CTZ切除猫中有一只在给予300mg/kg环磷酰胺后出现呕吐。由于环磷酰胺是一种不可预测的催吐刺激物，因此无法进一步评估CTZ切除对环磷酰胺诱导呕吐的影响。然而，给予200mg/kg磷酰胺氮芥的CTZ切除猫呕吐频率明显较低（卡方检验P = 0.05），且潜伏期比未切除的动物更长。在接受大于或等于3400mg/kg环磷酰胺的猫中观察到一种短暂的严重神经毒性反应，这可能对呕吐有抑制作用。发现磷酰胺氮芥是猫的一种强效催吐刺激物，可能是环磷酰胺给药后催吐反应的原因之一。对潜伏期数据的分析表明，在猫中其他环磷酰胺代谢产物也可能导致呕吐综合征。
