Effect of acyl chains of phosphatidylcholines on the pharmacokinetics of menatetrenone incorporated in O/W lipid emulsions prepared with phosphatidylcholines and soybean oil in rats.
Oil-in-water (O/W) lipid emulsions were prepared with phosphatidylcholines (PCs) of various acyl chains and soybean oil (SO) using a microfluidizer system, and the pharmacokinetics of menatetrenone incorporated in these oil particles were examined at the clinical injection volume (0.1 mL kg(-1)) in rats. The plasma half-life of menatetrenone incorporated in the oil particles prepared with SO and dipalmitoylphosphatidylcholine (DPPC) (SO/DPPC) was longer than that prepared with SO and eggyolk phosphatides (EYP) (SO/EYP) by 3 fold, while those of menatetrenone as oil particles prepared with SO and either dilauroyl phosphatidylcholine (DLPC), dimyristoyl phosphatidylcholine (DMPC), distearoyl phosphatidylcholine (DSPC), dioleoyl phosphatidylcholine (DOPC) or dilinoleoyl phosphatidylcholine (DLoPC) (SO/DLPC, SO/DMPC, SO/DSPC, SO/DOPC and SO/DLoPC, respectively) were similar to that of menatetrenone as SO/EYP. The menatetrenone uptake by the liver was not significantly different from that as SO/EYP in all SO/PCs examined, but the menatetrenone uptake by the spleen as SO/DPPC and SO/DSPC was higher than that as SO/EYP. The menatetrenone uptake by the lungs as SO/DPPC was also higher than that as SO/EYP. These findings suggest that SO/DPPC is a good candidate drug carrier for the prolonged plasma circulation of lipophilic drugs.
Ueda
Kumiko
K
Department of Pharmaceutics, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan. ueda@kobepharma-u.ac.jp
Fujimoto
Masanori
M
Noto
Hiromi
H
Sakaeda
Toshiyuki
T
Iwakawa
Seigo
S
D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D006207:Half-Life; D006490:Hemostatics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013024:Soybean Oil / Q000737:chemistry*; D014018:Tissue Distribution; D024482:Vitamin K 2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D006490:Hemostatics; D010713:Phosphatidylcholines; D024482:Vitamin K 2; C030814:menatetrenone; D013024:Soybean Oil