Maniez-Devos D M, Baurain R, Trouet A, Lesne M
J Pharmacol. 1986 Jan-Mar;17(1):14-20.
The pharmacokinetics of daunorubicinol (DOL), the main metabolite of daunorubicin (DNR), was studied in rabbits and compared to that of daunorubicin after an 8 mg/kg dose. High-performance liquid chromatography was used to separate parent drug and metabolites. The plasma disappearance of DNR and DOL was triexponential. DOL was the major species detected in plasma and urine. Both drugs had large volumes of distribution. About 70% of DNR or DOL were bound to plasma proteins and mainly to albumin. Pharmacokinetic parameters of DOL obtained after injection of DOL were different from those calculated for DNR and those calculated for DOL after injection of DNR. The total urinary excretions of DNR or DOL were similar and amounted to 25% of the dose. No conjugates were identified in urine after enzymatic treatment. No fluorescent drug was identified in the feces. Anthracyclines were degraded in vitro in rabbit feces. The rabbit seems to be a good model for the study of anthracycline pharmacokinetics as our results in rabbits after DNR injection were similar to those in human studies.
对柔红霉素醇（DOL）（柔红霉素（DNR）的主要代谢产物）在兔体内的药代动力学进行了研究，并与8mg/kg剂量的柔红霉素的药代动力学进行了比较。采用高效液相色谱法分离母体药物和代谢产物。DNR和DOL的血浆消除呈三指数型。DOL是血浆和尿液中检测到的主要成分。两种药物的分布容积都很大。约70%的DNR或DOL与血浆蛋白结合，主要是与白蛋白结合。注射DOL后获得的DOL药代动力学参数与注射DNR后计算出的DNR药代动力学参数以及计算出的DOL药代动力学参数不同。DNR或DOL的总尿排泄量相似，占剂量的25%。酶处理后尿液中未鉴定出结合物。粪便中未鉴定出荧光药物。蒽环类药物在兔粪便中体外降解。兔似乎是研究蒽环类药物药代动力学的良好模型，因为我们在兔体内注射DNR后的结果与人体研究结果相似。
