Effect of Oxyethylene Moieties in Hydrogenated Castor Oil on the Pharmacokinetics of Menatetrenone Incorporated in O/W Lipid Emulsions Prepared with Hydrogenated Castor Oil and Soybean Oil in Rats

• Published in: Journal of drug targeting Vol. 11; no. 1; pp. 37 - 43
• Main Authors: Ueda, Kumiko, Yamazaki, Yuka, Noto, Hiromi, Teshima, Yasuko, Yamashita, Chiharu, Sakaeda, Toshiyuki, Iwakawa, Seigo
• Format: Journal Article
• Language: English
• Published: Abington Informa UK Ltd 01.01.2003; Taylor & Francis
• Subjects: Animals; Biological and medical sciences; Castor Oil - administration & dosage; Castor Oil - analogs & derivatives; Castor Oil - chemistry; Chemistry, Pharmaceutical; Emulsions; General and cellular metabolism. Vitamins; General pharmacology; Hydrogenated castor oil; Hydrogenation; Lipid emulsions; Lipids; Male; Medical sciences; Menatetrenone; Oxyethylene; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rats; Rats, Wistar; Soybean Oil - administration & dosage; Soybean Oil - chemistry; Vitamin K 2 - analogs & derivatives; Vitamin K 2 - blood; Vitamin K 2 - pharmacokinetics; Water - administration & dosage; Pharmaceutical technology; Intravenous administration; Rat; Oil water emulsion; Rodentia; Lipids; Drug carrier; Menatetrenone; Hydrogenation; Blood plasma; Vertebrata; Mammalia; Lipid emulsions; Castor oil; Oxyethylene; Animal; Dosage form; Ethylene oxide; Soybean oil; Pharmacokinetics; Hydrogenated castor oil; Vitamin K
• ISSN: 1061-186X; 1029-2330
• DOI: 10.1080/1061186031000086081

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.