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.