Kovach J S, Eagan R T, Powis G, Rubin J, Creagan E T, Moertel C G
Cancer Treat Rep. 1981 Nov-Dec;65(11-12):1031-6.
DON, a glutamine antagonist, was administered iv to 26 patients with advanced cancer either once every 3 wks or daily for 3 days every 3 wks to determine toxicity and to look for evidence of therapeutic effect. Total doses ranged from 150 to 600 mg/m2. The single-day schedule produced intolerable nausea and vomiting and no evidence of cytotoxicity at 450-550 mg/m2 given over 10 mins or over 4 hrs. On the 3-day schedule, patients had tolerable gastrointestinal toxic effects at total doses up to 480 mg/m2 given in three equally divided doses by 10-min infusion. This dose also produced cytotoxic activity manifested as transient mild leukopenia and, rarely, thrombocytopenia. No objective responses were seen. Analysis of the plasma elimination of DON demonstrated dose-dependent pharmacokinetic behavior. The parent compound was not detectable in the urine of any patient, indicating extensive metabolism of the drug.
向26例晚期癌症患者静脉注射谷氨酰胺拮抗剂6-重氮-5-氧代-L-正亮氨酸（DON），给药方案为每3周1次或每3周连续3天每日1次，以确定毒性并寻找治疗效果的证据。总剂量范围为150至600mg/m²。单日给药方案会产生无法耐受的恶心和呕吐，在10分钟内或4小时内给予450-550mg/m²时未发现细胞毒性证据。在3天给药方案中，患者在通过10分钟输注以三等分剂量给予高达480mg/m²的总剂量时，出现了可耐受的胃肠道毒性作用。该剂量还产生了细胞毒性活性，表现为短暂性轻度白细胞减少，很少出现血小板减少。未观察到客观缓解。对DON的血浆消除分析表明其具有剂量依赖性药代动力学行为。在任何患者的尿液中均未检测到母体化合物，表明该药物有广泛的代谢。
