Dose-dependent pharmacokinetics of itraconazole after intravenous or oral administration to rats: intestinal first-pass effect
| Autor: | Yu C. Kim, Jee H. Shin, Ka Y. Choi, Myung Gyoon Lee |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
Antifungal Agents Itraconazole Duodenum Administration Oral Pharmacology Intestinal absorption Rats Sprague-Dawley First pass effect Pharmacokinetics Oral administration Medicine Animals Bile Pharmacology (medical) Intestinal Mucosa Intubation Gastrointestinal Gastric Juice Dose-Response Relationship Drug business.industry Portal Vein Half-life Bioavailability Rats Dose–response relationship Infectious Diseases Intestinal Absorption Area Under Curve Injections Intravenous business medicine.drug Half-Life |
| Zdroj: | Antimicrobial agents and chemotherapy. 48(5) |
| ISSN: | 0066-4804 |
| Popis: | 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 μg · 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 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 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. |
| Databáze: | OpenAIRE |
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