Dose-dependent pharmacokinetics of a new reversible proton pump inhibitor, DBM-819, after intravenous and oral administration to rats: hepatic first-pass effect

2001 ◽  
Vol 22 (3) ◽  
pp. 119-128 ◽  
Author(s):  
Eun J. Kim ◽  
Sun-O. Kim ◽  
Dong H. Lee ◽  
Hong Lim ◽  
Myung G. Lee
Keyword(s):  
Proton Pump Inhibitor ◽  
Oral Administration ◽  
Proton Pump ◽  
First Pass Effect ◽  
First Pass ◽  
Intravenous And Oral Administration ◽  
Dose Dependent

Gastrointestinal First-pass Effect of YJA-20379-8, a New Reversible Proton Pump Inhibitor, in Rats

1999 ◽  
Vol 51 (9) ◽  
pp. 1031-1036 ◽  
Author(s):  
JONGHAN KIM ◽  
EUN J. KIM ◽  
KYE S. HAN ◽  
MAN S. CHANG ◽  
MYUNG G. LEE
Keyword(s):  
Proton Pump Inhibitor ◽  
Proton Pump ◽  
First Pass Effect ◽  
First Pass

scholarly journals Dose-Dependent Pharmacokinetics of Tofacitinib in Rats: Influence of Hepatic and Intestinal First-Pass Metabolism

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 318 ◽  
Author(s):  
Ji Sang Lee ◽  
So Hee Kim
Keyword(s):  
Oral Administration ◽  
Intravenous Administration ◽  
Hepatic Metabolism ◽  
Time Curve ◽  
First Pass Effect ◽  
First Pass Metabolism ◽  
First Pass ◽  
Dose Dependent ◽  
Intraduodenal Administration ◽  
Pass Metabolism

This study investigated the pharmacokinetics of tofacitinib in rats and the effects of first-pass metabolism on tofacitinib pharmacokinetics. Intravenous administration of 5, 10, 20, and 50 mg/kg tofacitinib showed that the dose-normalized area under the plasma concentration-time curve from time zero to infinity (AUC) was significantly higher at 50 mg/kg than at lower doses, a difference possibly due to saturation of the hepatic metabolism of tofacitinib. Oral administration of 10, 20, 50, and 100 mg/kg tofacitinib showed that the dose-normalized AUC was significantly higher at 100 mg/kg than at lower doses, a difference possibly due to saturation of the intestinal metabolism of tofacitinib. Following oral administration of 10 mg/kg tofacitinib, the unabsorbed fraction from the rat intestine was 3.16% and the bioavailability (F) was 29.1%. The AUC was significantly lower (49.3%) after intraduodenal, compared to intraportal, administration, but did not differ between intragastric and intraduodenal administration, suggesting that approximately 46.1% of orally administered tofacitinib was metabolized through an intestinal first-pass effect. The AUC was also significantly lower (42%) after intraportal, compared to intravenous, administration, suggesting that the hepatic first-pass effect on tofacitinib after entering the portal vein was approximately 21.3% of the oral dose. Taken together, these findings suggest that the low F of tofacitinib is due primarily to intestinal first-pass metabolism.

scholarly journals Dose-Dependent Pharmacokinetics of Itraconazole after Intravenous or Oral Administration to Rats: Intestinal First-Pass Effect

2004 ◽  
Vol 48 (5) ◽  
pp. 1756-1762 ◽  
Author(s):  
Jee H. Shin ◽  
Ka Y. Choi ◽  
Yu C. Kim ◽  
Myung G. Lee
Keyword(s):  
Oral Dose ◽  
Oral Administration ◽  
Intragastric Administration ◽  
Time Curve ◽  
First Pass Effect ◽  
First Pass ◽  
Absolute Oral Bioavailability ◽  
Oral Doses ◽  
Dose Dependent ◽  
Intraduodenal Administration

ABSTRACT The dose-dependent pharmacokinetics of itraconazole after intravenous (10, 20, or 30 mg/kg) and oral (10, 30, or 50 mg/kg) administration and the first-pass effects of itraconazole after intravenous, intraportal, intragastric, and intraduodenal administration at a dose of 10 mg/kg were evaluated in rats. After intravenous administration at a dose of 30 mg/kg, the area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) was significantly greater than those at 10 and 20 mg/kg (1,090, 1,270, and 1,760 μg · min/ml for 10, 20, and 30 mg/kg, dose-normalized at 10 mg/kg). After oral administration, the AUC0-∞ was significantly different for three oral doses (380, 687, and 934 μg · min/ml for 10, 30, and 50 mg/kg, respectively, dose-normalized at 10 mg/kg). The extent of absolute oral bioavailability (F) was 34.9% after an oral dose at 10 mg/kg. The AUC0-∞ (or AUC0-8 h) values were comparable between intravenous and intraportal administration and between intragastric and intraduodenal administration, suggesting that the hepatic and gastric first-pass effects were almost negligible in rats. However, the AUC0-8 h values after intraduodenal and intragastric administration were significantly smaller than that after intraportal administration, approximately 30%, suggesting that the intestinal first-pass effect was approximately 70% of that of an oral dose of 10 mg/kg. The low F after oral administration of itraconazole at a dose of 10 mg/kg could be mainly due to the considerable intestinal first-pass effect.

Sign in / Sign up

Export Citation Format

Share Document