Dose-Independent Pharmacokinetics of a New Reversible Proton Pump Inhibitor, KR-60436, after Intravenous and Oral Administration to Rats: Gastrointestinal First-Pass Effect

Yu, Su-Yeon; Bae, Soo Kyung; Kim, Eun Jung; Kim, Yoon Gyoon; Kim, Sun‐Ok; Lee, Dong Ha; Lim, Hong; Lee, Myung Gull

doi:10.1002/jps.10427

Cited by 23 publications

(23 citation statements)

References 28 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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“…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.…”

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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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“…However, being below the detection limit of GI 24 h was not likely due to chemical and enzymatic degradation of theophylline in rats' gastric juices, because theophylline was stable for up to 24 h of incubation in various buffer solutions that had pHs ranging from 1 to 13 and for up to 4 h of incubation in four rats' gastric juices (pHs of 1.5, 1.5, 2.0, and 2.0, respectively). More than 91.8 and 94.5% of the spiked amounts of theophylline were recovered from various buffer solutions and rats' gastric juices, respectively, using a reported method (Yu et al, 2003). Kim et al (2003) reported that the contribution of the biliary excretion of unchanged theophylline to the CL NR of theophylline is almost negligible.…”

Section: Resultsmentioning

confidence: 99%

Time-Dependent Effects of Klebsiella Pneumoniae Endotoxin (KPLPS) on the Pharmacokinetics of Theophylline in Rats: Return of the Parameters in 96-Hour KPLPS Rats to the Control Levels

Yang

Jung²,

Lee³

et al. 2008

Drug Metab Dispos

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ABSTRACT:It has been reported that theophylline is primarily metabolized via hepatic CYP1A1/2, 2B1/2, and 3A1/2, and 1,3-dimethyluric acid (1,3-DMU) is primarily formed via CYP1A1/2 in rats. Compared with control rats, the expression of CYP1A subfamily, 2B1/2, and 3A subfamily significantly decreased 24 h (24-h KPLPS rats) after intravenous administration of lipopolysaccharide derived from Klebsiella pneumoniae (KPLPS) to rats but returned to that in control rats after 96 h (96-h KPLPS rats). After intravenous or oral administration of theophylline to 24-h KPLPS rats, the values for the total area under the plasma concentration-time curve from time zero to time infinity of theophylline and 1,3-DMU became significantly greater (46.5 and 34.0% increase after intravenous and oral administration, respectively) and smaller (36.3 and 21.6% decrease, respectively), respectively. Because theophylline is a low hepatic extraction ratio drug in rats, the above results could have been due to significantly slower CL int for the disappearance of theophylline and for the formation of 1,3-DMU (37.1 and 60.6% decrease, respectively). However, in 96-h KPLPS rats, the pharmacokinetic parameters of theophylline and 1,3-DMU returned fully or partially to those in control rats. These findings indicate the existence of time-dependent effects of KPLPS on the pharmacokinetics of theophylline and 1,3-DMU in rats.Theophylline, a bronchodilator, has widely been used for the management of acute bronchospasm associated with asthma or chronic obstructive pulmonary disease. It is metabolized to 1-methylxanthine (MX), 3-MX, and 1,3-dimethyluric acid (1,3-DMU), and 1-MX is further metabolized to 1-methyluric acid via xanthine oxidase in rats (McManus et al., 1988). Recently, Yang et al. (2008) reported that theophylline is primarily metabolized via hepatic microsomal cytochrome P450 (P450) 1A1/2, 2B1/2, and 3A1/2 (but not via CYP2C11, 2D6, and 2E1), and 1,3-DMU was primarily formed via CYP1A1/2 in male Sprague-Dawley rats.Lipopolysaccharide (LPS) is an active component in the outer membrane of Gram-negative bacteria. There have been several studies on changes in the expression of hepatic P450 isozymes in rats pretreated with LPS derived from Klebsiella pneumoniae (KPLPS) (Nadai et al., 1998;Ueyama et al., 2005). However, to our knowledge, no studies on changes in the expression of hepatic CYP1A subfamily, 2B1/2, and 3A subfamily in rats pretreated with KPLPS after 24 h (24-h KPLPS) and 96 h (96-h KPLPS) based on Western blot analysis have yet been reported. It has been reported that inflammation is triggered in rats by a small dose of LPS (Deng et al., 2006), bacterial infection is an important factor in bronchial asthma (Oehling, 1999), and Gram-negative bacterial infections are common in patients with chronic obstructive pulmonary disease combined with pneumonia (Yi et al., 2003). Thus, we examined theophylline in this study.The aim of this study was to investigate changes in pharmacokinetics of theophylline and 1,3-DMU after intravenous or o...

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Dose-Independent Pharmacokinetics of a New Reversible Proton Pump Inhibitor, KR-60436, after Intravenous and Oral Administration to Rats: Gastrointestinal First-Pass Effect

Cited by 23 publications

References 28 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-7867, a New Oxazolidinone, after Intravenous or Oral Administration to Rats: Intestinal First-Pass Effect

Time-Dependent Effects of Klebsiella Pneumoniae Endotoxin (KPLPS) on the Pharmacokinetics of Theophylline in Rats: Return of the Parameters in 96-Hour KPLPS Rats to the Control Levels

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