title: In vivo efficacy and tumor-selective metabolism of amrubicin to its active metabolite.
abstract: The tissue distribution of a novel antitumor anthracycline antibiotic, amrubicin, was studied using seven human tumor xenografts implanted into nude mice, in order to identify the principal factors determining its therapeutic efficacy. We found a good correlation between the level of the metabolite amrubicinol in the tumor and the in vivo efficacy. High metabolic activity of amrubicin to amrubicinol was detected in tumor tissue homogenates, especially in cell lines highly sensitive to amrubicin in vivo. In contrast to amrubicin, the administration of amrubicinol showed less tumor-selective toxicity in these human tumor xenograft models. These data indicate that the tumor-selective metabolism of amrubicin to amrubicinol resulted in a tumor-selective disposition of amrubicinol, leading to good efficacy in in vivo experimental therapeutic models.
authors.affiliation: Research Center, Sumitomo Pharmaceuticals Co., Ltd., Osaka.
authors.forename: T
authors.initials: T
authors.lastname: Noguchi
authors.forename: S
authors.initials: S
authors.lastname: Ichii
authors.forename: S
authors.initials: S
authors.lastname: Morisada
authors.forename: T
authors.initials: T
authors.lastname: Yamaoka
authors.forename: Y
authors.initials: Y
authors.lastname: Yanagi
mesh_terms: D000818:Animals; D018943:Anthracyclines / Q000493:pharmacokinetics / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001711:Biotransformation; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; C055866:amrubicin