Effect of particle size on the pharmacokinetics of menatetrenone incorporated in O/W lipid emulsions prepared with hydrogenated castor oils and soybean oil in rats.
Previously, we prepared lipid emulsions with soybean oil (SO; 20%) as oil phase and hydrogenated castor oils (HCOs; 2.4%) as emulsifiers (SO(20)/HCOs(2.4)), and found that the lipid emulsions prepared with HCO of 10 oxyethylene units (SO(20)/HCO10(2.4)) were quickly cleared from the plasma, while those prepared with HCO of 20 oxyethylene units (SO(20)/HCO20(2.4)) showed prolonged plasma circulation of the incorporated drug (Ueda et al., 2003). In the present study, the pharmacokinetics of menatetrenone incorporated into SO/HCO10s and SO/HCO20s of different particle sizes (100-280 nm), obtained by altering the SO contents, were examined in rats. The plasma half-lives of menatetrenone as SO/HCO10s were similar to each other, irrespective of particle size, even though the liver uptake of menatetrenone as SO(2.5)/HCO10(2.4) was larger than that as SO(20)/HCO10(2.4). The menatetrenone half-lives were also similar to each other for SO/HCO20s. The pretreatment with dextran sulfate 500,000 (DS500), a suppressor of the reticuloendothelial system (RES), increased the plasma concentration and inhibited the liver uptake of menatetrenone as SO/HCO10s, but not for those as SO/HCO20s. These findings indicated that the particle sizes did not affect the minimum oxyethylene units within HCOs for the prolonged plasma circulation of menatetrenone as SO/HCOs, which was 20.
Department of Pharmaceutics, Kobe Pharmaceutical University, Japan. ueda@kobepharma-u.ac.jp
Kumiko
K
Ueda
Yuka
Y
Yamazaki
Yasuko
Y
Teshima
Chiharu
C
Yamashita
Toshiyuki
T
Sakaeda
Seigo
S
Iwakawa
D000818:Animals; D002368:Castor Oil / Q000737:chemistry / Q000493:pharmacokinetics*; D005217:Fat Emulsions, Intravenous / Q000737:chemistry / Q000493:pharmacokinetics*; D006865:Hydrogenation; D008099:Liver / Q000378:metabolism; D008297:Male; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013024:Soybean Oil / Q000737:chemistry / Q000493:pharmacokinetics*; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*
D005217:Fat Emulsions, Intravenous; D024482:Vitamin K 2; C030814:menatetrenone; D013024:Soybean Oil; D002368:Castor Oil