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.
Tadano
K
K
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Yuzuriha
T
T
Sato
T
T
Fujita
T
T
Shimada
K
K
Hashimoto
K
K
Satoh
T
T
D000818:Animals; D001646:Bile / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008401:Gas Chromatography-Mass Spectrometry; D006868:Hydrolysis; D008099:Liver / Q000378:metabolism; D008297:Male; D008745:Methylation; D051381:Rats; D011919:Rats, Inbred Strains; D012588:Scintillation Counting; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D024482:Vitamin K 2 / Q000031:analogs & derivatives; D014859:Warfarin / Q000494:pharmacology
D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; D014859:Warfarin