Egorin M J, Van Echo D, Fox B M, Whitacre M, Bachur N R
Cancer Chemother Pharmacol. 1982;8(1):41-6. doi: 10.1007/BF00292870.
The plasma pharmacokinetics of the antineoplastic anthracycline antibiotic aclacinomycin A (Acm) and its metabolites were studied in 12 patients treated with 60-120 mg/m2 during a phase I clinical trial. Total plasma drug fluorescence initially declined very rapidly, but from 2 to 24 h after injection, fluorescence rose progressively to intensities greater than those measured 1 min after Acm injection. Plasma total drug fluorescence slowly declined from 24 to 72 hours after Acm administration. These events reflected the rapid disappearance of Acm and the subsequent appearance of two highly fluorescent metabolites. One metabolite co-chromatographed with and had a fluorescence spectrum identical to known metabolite F1 (bisanhydroaklavinone). The other metabolite did not co-chromatograph with any previously described Acm metabolite. This metabolite had a fluorescence spectrum unlike any previously described Acm metabolite and was not altered by treatment for 60 min with 0.2 N HCl at 100 degrees C or by treatment for 24 h at 37 degrees C with bacterial beta-glucuronidase or limpet aryl sulfatase.
在一项I期临床试验中，对12例接受60 - 120 mg/m²阿克拉霉素A（Acm）治疗的患者研究了抗肿瘤蒽环类抗生素阿克拉霉素A及其代谢产物的血浆药代动力学。血浆总药物荧光最初下降非常迅速，但在注射后2至24小时，荧光逐渐上升至强度高于Acm注射后1分钟测得的强度。在Acm给药后24至72小时，血浆总药物荧光缓慢下降。这些事件反映了Acm的快速消失以及随后两种高荧光代谢产物的出现。一种代谢产物与已知代谢产物F1（双脱水阿克拉酮）共色谱，且荧光光谱相同。另一种代谢产物与任何先前描述的Acm代谢产物都不共色谱。该代谢产物的荧光光谱不同于任何先前描述的Acm代谢产物，并且在100℃下用0.2 N HCl处理60分钟或在37℃下用细菌β-葡萄糖醛酸酶或帽贝芳基硫酸酯酶处理24小时后均未改变。
