Riggs C E, Benjamin R S, Serpick A A, Bachur N R
Clin Pharmacol Ther. 1977 Aug;22(2):234-41. doi: 10.1002/cpt1977222234.
A patient with a choledochal T tube and normal liver function received adriamycin as therapy for abdominal histiocytic lymphoma. Plasma, urine, and bile samples were collected after drug administration. Adriamycin and its metabolites were extracted from the samples and separated by thin-layer chromatography. The pharmacokinetics of adriamycin and metabolites in plasma urine resembled those of previous patients, with a plasma elimination half-life for adriamycin of 25.2 hr. Bile contained adriamycin and 11 metabolites, 4 of which were not present in plasma or urine. Forty-one percent of the administered dose of adriamycin appeared in the bile in 7 days; of this amount, 42% was adriamycin, 22% was adriamycinol, the major metabolite, and 36% was other metabolites. Hepatic clearances of adriamycin and adriamycinol showed early, rapid removal of drug by the liver, with subsequent slowing of removal rate as plasma drug concentration declined. Adriamycin was more efficiently cleared than adriamycinol by both liver and kidney. Disease states which impair the capacity of the liver to excrete adriamycin may result in prolonged, high drug levels and increased toxicity.
一名带有胆总管T形管且肝功能正常的患者接受阿霉素治疗腹部组织细胞淋巴瘤。给药后采集血浆、尿液和胆汁样本。从样本中提取阿霉素及其代谢物,并通过薄层色谱法进行分离。阿霉素及其代谢物在血浆和尿液中的药代动力学与之前的患者相似,阿霉素的血浆消除半衰期为25.2小时。胆汁中含有阿霉素和11种代谢物,其中4种在血浆或尿液中不存在。给药剂量的41%的阿霉素在7天内出现在胆汁中;其中,42%是阿霉素,22%是主要代谢物阿霉素醇,36%是其他代谢物。阿霉素和阿霉素醇的肝脏清除率显示肝脏早期快速清除药物,随后随着血浆药物浓度下降清除率减慢。肝脏和肾脏对阿霉素的清除效率均高于阿霉素醇。损害肝脏排泄阿霉素能力的疾病状态可能导致药物水平长时间居高不下并增加毒性。