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

Kim, Jonghan; Kim, Eun J.; Han, Kyung-Sook; Chang, Man Sik; Lee, Myung G.

doi:10.1211/0022357991773519

Cited by 15 publications

(11 citation statements)

References 11 publications

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“…However, after intragastric and intraduodenal instillation of itraconazole at a dose of 10 mg/kg, the AUC 0-ϱ values for itraconazole were 29.9 and 26.0%, respectively, of that after intraportal administration, suggesting that the intestinal first-pass effect of itraconazole are approximately 70% of the oral dose in rats. Considerable intestinal first-pass effects of furosemide (13), azosemide (16), YH439 (a new hepatoprotective agent) (17), YJA-20379-8 (a new proton pump inhibitor) (18), ipriflavone (20), bumetanide (14), KR-31543 (a new neuroprotective agent for ischemia-reperfusion damage) (24), SR-4668 (a candidate for diabetic neuropathy) (15), KR-60436 (a new reversible proton pump inhibitor) (32), and DA-7867 (a new oxazolidinone antibiotic) (2) in rats, and midazolam (28) and saquinavir (8) in humans have been reported.…”

Section: Discussionmentioning

confidence: 99%

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

Shin

Choi

Kim

et al. 2004

Antimicrob Agents Chemother

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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 (AUC 0-ؕ ) was significantly greater than those at 10 and 20 mg/kg (1,090, 1,270, and 1,760 g ⅐ min/ml for 10, 20, and 30 mg/kg, dose-normalized at 10 mg/kg). After oral administration, the AUC 0-ؕ was significantly different for three oral doses (380, 687, and 934 g ⅐ min/ml for 10, 30, and 50 mg/kg, respectively, dosenormalized at 10 mg/kg). The extent of absolute oral bioavailability (F) was 34.9% after an oral dose at 10 mg/kg. The AUC 0-ؕ (or AUC 0-8 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 AUC 0-8 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.The pharmacokinetics of itraconazole after oral administration to humans (10-12), rats (11,22,31), and rabbits, cats, and dogs (11) have been reported; however, data on the pharmacokinetics after intravenous administration to humans (12), dogs (11), and rats (22, 31) are scarce. It has been reported (12) that after oral administration of itraconazole to humans, the values for the area under the plasma concentration-time curve from time zero to infinity (AUC 0-ϱ ) for the drug were dose dependent (increased in proportion to dose increases); 50, 100, and 200 mg by capsule after a meal and 100 and 200 mg by capsule after breakfast. However, the dose-dependent pharmacokinetics of itraconazole after intravenous administration and the first-pass effects of the drug have not been reported. It has been reported (31) that the hepatic first-pass effect of itraconazole was estimated to be 18.5% in rats.The purpose of this paper is to report the dose-dependent pharmacokinetics of itraconazole after intravenous (at doses of 10, 20, and 30 mg/kg) and oral (at doses of 10, 30, and 50 mg/kg) administration to rats and the intestinal first-pass effect of itraconazole after intravenous, intraportal, intragastric, and intraduodenal administration (at a dose of 10 mg/kg) to rats. MATERIALS AND METHODSChemicals. Sporanox intravenous solution (10 mg/ml as itraconazole as a solution in hydroxylpropyl-␤-cyclodextrin [HP-␤-CD], sorbitol, propylene glycol, HCl, NaOH, and water for injection; lot no. 01-D01A-IW), Spor...

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Section: Discussionmentioning

confidence: 99%

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

Shin

Choi

Kim

et al. 2004

Antimicrob Agents Chemother

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“…Hence, the hepatic first-pass effect for DA-8159 (i.e., 23%) is equivalent to $9% of the oral dose. Considerable intestinal first-pass effect for furosemide, 19 bumetanide, 20 KR-31543 (a new neuroprotective agent for ischemia-reperfusion damage), 21 azosemide, 9 YH439 (a new hepatoprotective agent), 22 YJA-20379-8 (a new reversible proton pump inhibitor), 23 ipriflavone, 24 SR-4668 (a candidate for diabetic neuropathy), 25 and KR-60436 (a new reversible proton pump inhibitor, our unpublished data) in rats and midazolam 26 and saquinavir 27 in humans has been reported.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of DA‐8159, a New Erectogenic, after Intravenous and Oral Administration to Rats: Hepatic and Intestinal First‐Pass Effects

Shim

Kim

Park

et al. 2003

Journal of Pharmaceutical Sciences

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“…However, the AUC 0-ϱ after an intraduodenal administration was 76.3% of that after an intraportal administration, suggesting that the intestinal first-pass effect of DA-7867 could be approximately 21.8% [(100 Ϫ 76.3) ϫ (1 Ϫ 0.0827)] of the oral dose. The considerable intestinal first-pass effects of furosemide (12), azosemide (14), YH439 (a new hepatoprotective agent) (15), YJA-20379-8 (a new reversible proton pump inhibitor) (16), ipriflavone (18), bumetanide (11), KR-31543 (a new neuroprotective agent for ischemia-reperfusion damage) (20), SR-4668 (a candidate for diabetic neuropathy) (13), KR-60436 (a new reversible proton pump inhibitor) (22), and oltipraz (our unpublished data) in rats and midazolam (21) and saquinavir (8) in humans have been reported.…”

mentioning

confidence: 99%

Pharmacokinetics of DA-7867, a New Oxazolidinone, after Intravenous or Oral Administration to Rats: Intestinal First-Pass Effect

Bae

Chung

Kim

et al. 2004

Antimicrob Agents Chemother

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Pharmacokinetic parameters of DA-7867 were dose independent after both intravenous administration and oral administration (at doses of 1 to 20 mg/kg of body weight) to rats. After oral administration of DA-7867 to rats at a dose of 10 mg/kg, approximately 8.27% of oral dose was not absorbed from the gastrointestinal tract, F was 70.8%, and approximately 21.8% of the oral dose was eliminated by the intestine (intestinal first-pass effect).During the 1980s and 1990s, the emergence and wide spread of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE; Enterococcus faecium and MICs at which 90% of isolates tested are inhibited (MIC 90 s) of DA-7867 were 0.78, 0.2, and 0.39 g/ml for MRSA (n ϭ 37), VRE (E. faecium; n ϭ 36), and PRSP (n ϭ 33), and the corresponding values for linezolid were 3.13, 1.56, and 1.56 g/ml. The MIC 90 s of DA-7867 were 3.13 and 0.78 g/ml for H. influenzae (n ϭ 37) and M. catarrhalis, respectively, which were four-to eightfold lower than those of linezolid. DA-7867 is being evaluated in preclinical studies as a new oxazolidinone antibiotic. The purpose of the present study was to report the dose-independent area under the plasma drug concentrationtime curve from time zero to time infinity (AUC 0-ϱ ) of DA-7867 after intravenous or oral administration to rats of doses of 1, 5, 10, and 20 mg/kg and gastric and intestinal first-pass effects of DA-7867 after intraportal, intragastric, and intraduodenal administration to rats of a dose of 10 mg/kg.DA - Other chemicals were of reagent or HPLC grade and therefore were used without further purification. Male Sprague-Dawley rats (weight, 264 to 310 g) were purchased from Charles River Company Korea (Biogenomics, Seoul, Korea). The animals were maintained in a clean room

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

Cited by 15 publications

References 11 publications

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

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

Pharmacokinetics of DA‐8159, a New Erectogenic, after Intravenous and Oral Administration to Rats: Hepatic and Intestinal First‐Pass Effects

Pharmacokinetics of DA-7867, a New Oxazolidinone, after Intravenous or Oral Administration to Rats: Intestinal First-Pass Effect

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