Identification of menaquinone-4 metabolites in the rat

Abstract

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-l, 4-naphthoquinone [K acid 2]. The aglycone of a third minor metabolite isolated from bile was tentatively identified as 2-methyi-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 ω- and β-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. © 1989, The Pharmaceutical Society of Japan. All rights reserved.