Science Links Japan | Studies on the Metabolic Fate of Amrubicin Hydrochloride(SM-5887), a Novel Antitumor Agent (6)-Pharmacokinetic Studies of Amrubicinol, the Major Bioactive Metabolite of Amrubicin, in Rats.

Studies on the Metabolic Fate of Amrubicin Hydrochloride(SM-5887), a Novel Antitumor Agent (6)-Pharmacokinetic Studies of Amrubicinol, the Major Bioactive Metabolite of Amrubicin, in Rats.

Accession number;99A0241102

Title;Studies on the Metabolic Fate of Amrubicin Hydrochloride(SM-5887), a Novel Antitumor Agent (6)-Pharmacokinetic Studies of Amrubicinol, the Major Bioactive Metabolite of Amrubicin, in Rats.

Author; NAKAI SHUNJI (Sumitomo Chemical Co., Ltd.) AKAO KYOKO (Sumitomo Chemical Co., Ltd.) ITO MASAKI (Sumitomo Chemical Co., Ltd.) KANAMARU HIROSHI (Sumitomo Chemical Co., Ltd.) NAKATSUKA IWAO (Sumitomo Chemical Co., Ltd.)

Journal Title;Japanese Pharmacology & Therapeutics

Journal Code:Z0947A

ISSN:0386-3603

VOL.27;NO.Suppl.1;PAGE.S.531-S.543(1999)

Figure&Table&Reference;FIG.5, TBL.5, REF.12

Pub. Country;Japan

Language;Japanese

Abstract;Pharmacokinetic studies on plasma and blood cells concentrations, tissue distribution and excretion of amrubicinol(SM-5887-13-OH), the major bioactive metabolite of SM-5887, were performed after a single intravenous administration of 14C-labeled SM-5887-13-OH at a dose of 5mg/kg to rats. 1) The radioactivity concentrations in plasma and blood cells decreased rapidly until 1hr after administration, thereafter increased at 24hr, and decreased again slowly. The levels of radioactivity in blood cells were 0.6-3 of those in plasma. 2) Plasma and blood cells concentrations of SM-5887-13-OH decreased multi-exponentially. The levels of SM-5887-13-OH in blood cells were at least 6 times as high as those in plasma. The .ALPHA.,.BETA. and .GAMMA.-phase half-lives of SM-5887-13-OH concentration in plasma were 0.36min, 9.6min and 3.88hr, respectively. 3) In plasma and blood cells, aglycone metabolites such as Met A, Met B and Met C were detected. 4) The radioactivity concentrations in most tissues reached maxima at 1-4hr after administration, whereas the concentrations in submaxillary gland, Harderian gland, thymus, plasma and hair, reached maxima at 24hr after administration. The radioactivity concentrations in many tissues were higher than those in plasma, and the concentrations were relatively high in bone marrow, spleen, kidney, pancreas, liver, submaxillary gland, Harderian gland and pituitary at 1-24hr after administration, and in submaxillary gland and pituitary at 168hr after administration. The radioactivities in submaxillary gland, testis and hair disappeared slowly, although they were in a relatively low levels. 5) The tissue concentrations of SM-5887-13-OH were high in pancreas, spleen, submaxillary gland, small intestine and bone marrow. The concentrations of Met B, the major metabolite in tissues, were very high in liver, kidney and adrenal.... (author abst.)

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