Creaven P J, Allen L M, Alford D A
J Pharm Pharmacol. 1975 Dec;27(12):914-8. doi: 10.1111/j.2042-7158.1975.tb10247.x.
The bioavailability of the antineoplastic agent, ICRF-159, has been examined in 12 patients receiving the drug in single and subdivided dose schedules in an attempt to account for the differences in toxicity found with the different schedules clinically. Recovery of radioactivity in the urine after single large doses (13.3-19.4 g) was 8.5 +/- 3.0% of the administered dose. After doses of 3.8-5.55 g recovery was 22.7 +/- 10.5% and after the same dose subdivided into 3 equal aliquots it was 52 +/- 8.7%. Unrecovered radioactivity was largely accounted for in the faeces. Plasma radioactivity levels in 2 patients after high and low dose were equivalent. Toxicity of the drug paralleled urinary recovery of radioactivity. It is concluded that schedule dependence of toxicity of ICRF-159 is at least partly due to bioavailability factors.
已对12例接受抗肿瘤药物ICRF - 159的患者进行了生物利用度研究，这些患者接受了单次给药和分次给药方案，旨在解释临床上不同给药方案所发现的毒性差异。单次大剂量（13.3 - 19.4 g）给药后，尿液中放射性的回收率为给药剂量的8.5±3.0%。剂量为3.8 - 5.55 g时，回收率为22.7±10.5%，将相同剂量分为3等份给药后，回收率为52±8.7%。未回收的放射性主要存在于粪便中。2例患者在高剂量和低剂量给药后的血浆放射性水平相当。该药物的毒性与尿液中放射性的回收率平行。得出的结论是，ICRF - 159毒性的给药方案依赖性至少部分归因于生物利用度因素。
