Pharmacokinetics of ipriflavone, an isoflavone derivative, after intravenous and oral administration to rats - Hepatic and intestinal first-pass effects

被引:41
作者
Kim, SH
Lee, MG
机构
[1] Seoul Natl Univ, Coll Pharm, Kwanak Gu, Seoul 151742, South Korea
[2] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul 151742, South Korea
[3] Kangnung Natl Univ, Coll Dent, Kangnung 210702, South Korea
关键词
ipriflavone; M1; M5; pharmacokinetics; hepatic first-pass effects; intestinal first pass effects; rats;
D O I
10.1016/S0024-3205(01)01508-9
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Pharmacokinetic parameters of ipriflavone were evaluated after intravenous administration of spray-dried ipriflavone with polyvinylpyrrolidone, SIP (5, 10, 20, and 40 mg/kg as ipriflavone) and oral administration of SIP (50, 100, and 200 mg/kg as ipriflavone) to rats. The hepatic, gastric, and intestinal first-pass effects of ipriflavone were also measured after intravenous, intraportal, intraduodenal, and oral administration of SIP (20 or 50 mg/kg as ipriflavone) to rats. After intravenous and oral administration, the pharmacokinetic parameters of ipriflavone were dose-independent. The extent of absolute oral bioavailability (F) was also independent of oral doses; the mean F value was approximately 24%. Considering the amount of unchanged ipriflavone recovered from 24-hr gastrointestinal tract (the mean value was approximately 12%), the low F values could be due to the hepatic, gastric, and/or intestinal first-pass effects. Based on total body clearance (CL) data of ipriflavone after intravenous administration, the first-pass effect in the heart and lung could be almost negligible, if any, in rats. Approximately 30% of ipriflavone absorbed into the portal vein was eliminated by liver (hepatic first-pass effect) based on intravenous and intraportal administration of SIP. The area under the plasma concentration-time curve from time zero to time infinity (AUC) values after oral administration and intraduodenal instillation of SIP, 50 mg/kg as ipriflavone, were not significantly different, but the values were significantly smaller (129 and 116 mug ml/min) than that after intraportal administration of SIP, 20 mg/kg as ipriflavone (513 mug ml/min based on 50 mg/kg), indicating that gastric first-pass effect of ipriflavone was negligible, but intestinal first-pass effect was considerable in rats. Therefore, the low F value of ipriflavone after oral administration to rats was mainly due to intestinal first-pass effect. The hepatic first-pass effect and incomplete absorption of ipriflavone from rat gastrointestinal tract could also contributed to the low F in rats. (C) 2002 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:1299 / 1315
页数:17
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