Pharmacokinetics of ipriflavone, an isoflavone derivative, after intravenous and oral administration to rats hepatic and intestinal first-pass effects.
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 microg ml/min) than that after intraportal administration of SIP, 20 mg/kg as ipriflavone (513 microg 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.
Kim
So Hee
SH
College of Dentistry, Kangnung National University, Kangnung, Korea.
Lee
Myung Gull
MG
D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism*; D007275:Injections, Intravenous; D007529:Isoflavones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000700:Analgesics; D007529:Isoflavones; C018986:ipriflavone