抄録
The metabolic fate of 9, 3"-diacetylmidecamycin (MOM) was studied in several animal species and in man. The metabolites were isolated from the urine, bile, and incubation mixture of rat liver homogenate and characterized by mass and nuclear magnetic resonance spectra. The first step in the metabolic pathway of MOM has been shown to be a hydrolysis of an ester moiety in the 4"position, followed by spontaneous migration of an acyl group from 3"to 4"position, thereby forming 9, 4"-diacetylmidecamycin (Mb-1). The next step is a deacylation of 4"-acetyl group of Mb-1, to give 9-acetyl-4"-depropionylmidecamycin (Mb-2) ; Mb-2 is then hydroxylated to Mb-3 and Mb-5 (the diastereoisomers which differ only in the stereochemistry at C-14). In animals, the main metabolic route has been demonstrated to be as follows : MOM→Mb-1→Mb-2→Mb-3 and Mb-5. The other metabolic pathway of Mb-1 is a deacylation of 9-acetyl group to give 4"-acetyl-4"depropionylmidecamycin (Mb-12). Mb-12 is then hydroxylated at C-14 and/or deacetylated at 4". This latter metabolism has been shown to be a main course in man. In rat, about 14 and 28% as metabolites of the administered drug, respectively, have been shown to be excreted in the urine and bile. The parent antibiotic was detected neither in the urine, bile, nor in blood. Though about 1/3 of the total metabolites was detected as conjugated forms in the rat bile, the conjugates were excreted in a quite small amount (1-2% of the total urinary metabolites), in the case of the rat urine.
