Prolonged circulation of menatetrenone by emulsions with hydrogenated castor oils in rats.
Previously, we reported that plasma half-lives of a drug incorporated in lipid emulsions prepared with soybean oil (SO), a long-chain triglyceride, and hydrogenated castor oils (HCOs) (SO/HCOs) were markedly longer, while those as SO/polyoxyethylene sorbitan esters (SO/PSs) were similar, compared to that as SO/egg yolk phosphatides (SO/EYP) [J. Pharm. Pharmacol. 54 (2002) 1357; J. Drug Target. 11 (2003) 37]. In the present study, lipid emulsions were prepared with Miglyol 812 (MO), a medium-chain triglyceride, and HCOs, and the kinetics of the incorporated drug, menatetrenone, were examined. The plasma half-lives and the liver uptake of menatetrenone as MO/polyoxyethylene-(10)-hydrogenated castor oils (MO/HCO10s) were similar to and larger than those as MO/EYP, respectively. On the other hand, the plasma half-lives and liver uptake of menatetrenone as MO/polyoxyethylene-(20)-hydrogenated castor oils (MO/HCO20s) or MO/polyoxyethylene-(60)-hydrogenated castor oils (MO/HCO60s) were markedly longer and lower than those as MO/EYP, respectively. The pretreatment of dextran sulfate 500,000, a reticuloendothelial system suppressor, raised the plasma concentration and inhibited liver uptake of menatetrenone as MO/HCO10, but not for MO/HCO20. These findings suggest that the minimum number of oxyethylene units within HCOs for the prolonged plasma circulation of menatetrenone was 20 for MO/HCOs, similarly to SO/HCOs.
Ueda
Kumiko
K
Department of Pharmaceutics, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada, Kobe 658-8558, Japan. ueda@kobepharma-u.ac.jp
Furukawa
Takashi
T
Kawaguchi
Yuriko
Y
Miki
Yosuke
Y
Sakaeda
Toshiyuki
T
Iwakawa
Seigo
S
D000818:Animals; D019540:Area Under Curve; D002368:Castor Oil / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004655:Emulsions; D006207:Half-Life; D006490:Hemostatics / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006865:Hydrogenation; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010316:Particle Size; D010592:Pharmaceutic Aids; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014280:Triglycerides / Q000378:metabolism; D024482:Vitamin K 2 / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D004655:Emulsions; D006490:Hemostatics; D010592:Pharmaceutic Aids; D014280:Triglycerides; D024482:Vitamin K 2; C030814:menatetrenone; D002368:Castor Oil