Identification of menaquinone-4 metabolites in the rat

Four metabolites of menaquinone-4 [MQ-4] were isolated from rat urine, bile and liver. From rat urine following intravenous or oral administration of [14C]MQ-4, two major metabolites were isolated and their aglycones were identified as 2-methyl-3-(5'-carboxy-3'-methyl-2'-pentyl)-1,4-naphthoquinone [K acid 1] and 3-(3'-carboxybutyl)-2-methyl-1,4-naphthoquinone [K acid 2]. The aglycone of a third minor metabolite isolated from bile was tentatively identified as 2-methyl-3-(15'-carboxy-3',7',11'-trimethyl-2',6',10', 14'-hexadecatetranyl)-1,4-naphthoquinone [MQ-4-COOH]. The structures of the three aglycones, which were excreted into the urine or bile mainly as glucuronide conjugates, indicated that oxidative degradation of the alkyl side chain of MQ-4 had occurred by omega- and beta-oxidation. In addition, 2,3-epoxy-MQ-4 was identified in the liver of rats which were pretreated with warfarin and then dosed with [14C]MQ-4.