Effect of solubilizer on the metabolic fate of menaquinone-4 in rats.
Following intravenous administration to rats of all-trans [14C]menaquinone-4 solubilized with purified soybean lecithin [L] or with HCO-60 [H], we examined the effect of the solubilizers on the distribution and excretion of menaquinone-4 [MQ-4]. The level of radioactivity in the liver after dosing with L was about 2 times higher than in dosing with H, and a similar result was obtained in the hepatic microsomal fraction, a target of MQ-4. The rate and amount of biliary excretion of radioactivity after dosing with L were greater than in dosing with H. In addition, the uptake of [14C]MQ-4 by the isolated perfused rat liver was greater with L than H, consistent with the in vivo observation. Further, upon incubation of L or H with hepatic microsomes, the MQ-4 metabolizing enzyme was more highly active toward L than H. These results show that L is more easily transported to the target region, and more rapidly metabolized and excreted into the bile than H, suggesting that the lecithin-solubilized preparation of MQ-4 may be more effective clinically.
Tadano
K
K
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Yuzuriha
T
T
Ikeuchi
T
T
Sato
T
T
Fujita
T
T
D000818:Animals; D001646:Bile / Q000378:metabolism; D002368:Castor Oil / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010316:Particle Size; D010477:Perfusion; D010713:Phosphatidylcholines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012588:Scintillation Counting; D013501:Surface-Active Agents / Q000494:pharmacology*; D014018:Tissue Distribution; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000494:pharmacology; D024482:Vitamin K 2 / Q000031:analogs & derivatives
D010713:Phosphatidylcholines; D013501:Surface-Active Agents; D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; C023040:polyethoxylated castor oil; D002368:Castor Oil