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Dose-Dependent Pharmacokinetics of Itraconazole after Intravenous or Oral Administration to Rats: Intestinal First-Pass Effect. Jee H. Shin, 2004.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 .
Repressor Mutant Forms of the Azospirillum brasilense NtrC Protein. Luciano F. Huergo, 2004.
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