Iguchi H, Matsushita Y, Ohmori K, Hirano S, Kiyosaki T, Hori S, Tone H, Oki T
Jpn J Antibiot. 1980 Feb;33(2):179-91.
An anthracycline antitumor antibiotic, aclacinomycin A, was given to mice, rabbits or dogs intravenously to study the pharmacokinetics by photometric assay based on the absorption of anthracycline ring. The drug was rapidly eliminated from the blood in these animals. Drug levels were much higher in the blood cells than in the plasma. Tissue levels in dogs were 50 approximately 100 times higher than the blood levels, which showed the drug was rapidly transferred from the blood to tissues after administration. Higher levels were observed in the lungs, spleen and lymph nodes, where the drug was present as aclacinomycin A itself and the glycoside-type metabolites that were biologically active. The active form was also detected in the pancreas, heart, thymus, bone marrow and gastrointestinal tract. In the liver and kidneys, biologically inactive aglycone-type metabolites were observed. About 2 approximately 4% of the drug given to rabbits or dogs was recovered in the urine by 72 hours after administration, in which only 10% of the excreted drug was active form in rabbits but about 65% in dogs. The rest was inactive aglycone-type metabolites that were excreted almost in the conjugated form. Biliary excretion also contributed to the total clearance of the drug. Aclacinomycin A was absorbed even by oral administration in rabbits and dogs. Tissue distribution of the drug orally given to dogs was similar to that in intravenous administration, except that higher levels of active form were detected in the gastrointestinal tract and of inactive form in the liver.
将一种蒽环类抗肿瘤抗生素阿克拉霉素A静脉注射给小鼠、兔子或狗,通过基于蒽环环吸收的光度测定法研究其药代动力学。该药物在这些动物体内从血液中迅速消除。血细胞中的药物水平比血浆中的高得多。狗体内的组织水平比血液水平高约50至100倍,这表明给药后药物迅速从血液转移到组织中。在肺、脾和淋巴结中观察到较高水平,药物以阿克拉霉素A本身及其具有生物活性的糖苷型代谢物的形式存在。在胰腺、心脏、胸腺、骨髓和胃肠道中也检测到了活性形式。在肝脏和肾脏中,观察到了无生物活性的苷元型代谢物。给兔子或狗给药后72小时内,约2%至4%的药物在尿液中被回收,其中在兔子体内排泄的药物中只有10%是活性形式,而在狗体内约为65%。其余的是几乎以结合形式排泄的无活性苷元型代谢物。胆汁排泄也对药物的总清除有贡献。阿克拉霉素A在兔子和狗中口服时也能被吸收。给狗口服该药物后的组织分布与静脉给药相似,只是在胃肠道中检测到较高水平的活性形式,在肝脏中检测到较高水平的无活性形式。