Abstract
Lipid emulsions with particle sizes of 190–270 nm were prepared with soybean oil (SO) and a series of hydrogenated castor oils (HCOs) with various oxyethylene numbers, and the effect of oxyethylene numbers of HCOs on the pharmacokinetics of menatetrenone incorporated into the lipid emulsions was studied in rats. Plasma half-life of menatetrenone after administration as the lipid emulsions prepared by HCO with 10 oxyethylene units (SO/HCO10) was similar to that after the administration as SO/egg yolk phosphatides (SO/EYP), but was shorter than that as the lipid emulsions prepared by HCOs with >20 oxyethylene units (SO/HCO20, SO/HCO30, SO/HCO60 and SO/HCO100). Menatetrenone incorporated in SO/HCO10, SO/HCO20 and SO/HCO60 was not taken up by the blood cells in vitro, and the plasma level of menatetrenone incorporated in SO/HCO10 was similar to that of triglycerides, suggesting that menatetrenone was not released from the oil particles even after entering the circulation. Menatetrenone uptake by the liver for SO/HCO10 was similar to that for SO/EYP, while those for SO/HCO20, SO/HCO30, SO/HCO60 and SO/HCO100 was less than that for SO/EYP. These findings clearly demonstrate that 20 oxyethylene units in HCOs is the minimum requirement for the prolongation of the plasma circulation time of menatetrenone incorporated in SO/HCOs.
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