Hepatobiliary excretion of fluconazole and its interaction with cyclosporin A in rat blood and bile using microdialysis
| Autor: | Pen Ho Yeh, Tung Hu Tsai, Chen-Hsen Lee |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Microdialysis Antifungal Agents Femoral vein Pharmaceutical Science Pharmacology Rats Sprague-Dawley Pharmacokinetics Jugular vein Cyclosporin a medicine Animals Bile Drug Interactions Fluconazole Chromatography High Pressure Liquid Bile duct Chemistry Drug interaction Rats medicine.anatomical_structure Liver Area Under Curve Cyclosporine Immunosuppressive Agents medicine.drug |
| Zdroj: | International journal of pharmaceutics. 241(2) |
| ISSN: | 0378-5173 |
| Popis: | In order to investigate the hepatobiliary excretion of Fluconazole, we develop a rapid and sensitive method using high-performance liquid chromatography coupled with microdialysis for the simultaneous determination of unbound fluconazole in rat blood and bile. Microdialysis probes were inserted into both the jugular vein toward the right atrium and bile duct of male Sprague-Dawley rats for biological fluid sampling after administration of fluconazole at 10 mg/kg through the femoral vein. Fluconazole and dialysates were separated using a Zorbax phenyl column maintained at ambient temperature. The detection limit of fluconazole was 50 ng/ml. Biological fluid sampling thereby allowed the simultaneous determination of fluconazole levels in blood and bile. The disposition of fluconazole in the blood and bile fluid suggests that there was rapid exchange and equilibration between the blood and hepatobiliary system. In addition, to investigate the mechanism of P-glycoprotein related hepatobiliary excretion of fluconazole, we examined the drug-drug interaction of fluconazole and cyclosporin A in the aspect of pharmacokinetics. These results indicate that the plasma level of fluconazole was no different than that in bile, and that fluconazole undergoes hepatobiliary excretion, maybe unrelated to the P-glycoprotein transported system. |
| Databáze: | OpenAIRE |
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