Hulhoven R, Harvengt C
Pharmacology. 1982;24(4):253-60. doi: 10.1159/000137604.
The tissue distribution of daunorubicin (DNR) was investigated in rabbits after 5 mg/kg DNR i.v. bolus injection or 4 h infusion of 5 mg/kg either as free drug or as a complex with DNA. After i.v. bolus, the highest DNR concentration was observed in lungs and kidneys, a lower concentration in heart and spleen and the least in the liver. The DNR biotransformation to daunorubicinol (DNR-ol) and aglycones was most active in kidneys and liver, while heart, lungs and spleen metabolized DNR to a lower extent. The DNR tissue elimination half-life varied from 4.5 to 8.7 h, whereas concentrations of DNR-ol remained elevated for a longer period of time. After 4 h infusion, the only difference when compared with i.v. bolus consisted of a 3-fold lower initial DNR concentration in heart and lungs. No striking difference could be observed after free versus complexed drug infusion except for a somewhat lower DNR concentration in heart and lungs for the complexed drug.
在兔体内静脉推注5mg/kg柔红霉素(DNR)或静脉输注5mg/kg游离药物或与DNA复合物4小时后,研究了柔红霉素(DNR)的组织分布。静脉推注后,肺和肾中DNR浓度最高,心脏和脾脏中浓度较低,肝脏中浓度最低。DNR向柔红霉醇(DNR-ol)和苷元的生物转化在肾脏和肝脏中最活跃,而心脏、肺和脾脏对DNR的代谢程度较低。DNR在组织中的消除半衰期为4.5至8.7小时,而DNR-ol的浓度在较长时间内保持升高。静脉输注4小时后,与静脉推注相比,唯一的差异是心脏和肺中初始DNR浓度降低了3倍。游离药物与复合药物输注后未观察到明显差异,只是复合药物在心脏和肺中的DNR浓度略低。