OBJECTIVES: A "cocktail" of several substrates is frequently used to assess metabolic activity of multiple cytochrome P450 enzymes in one session. Some interactions among substrates can appear and may influence the rate of biotransformation of other ones. Our current work was aimed on the influence of tolbutamide on cytochrome P450-mediated metabolism of phenacetin and vice versa. DESIGN: In the presented work, the biotransformation rates of phenacetin and tolbutamide (markers of rat CYP1A2 and CYP2C6/11 metabolic activities, respectively) administered either separately or both simultaneously were compared. The model of isolated perfused rat liver was used. RESULTS: Phenacetin had no significant effect on tolbutamide hydroxylation. Tolbutamide addition to the perfusion medium significantly increased the rate of O-deethylation of phenacetin. CONCLUSION: Some differences in the rate of P450-mediated metabolism can be observed when comparing assessment using combination of two model substrates with the common way (single marker administration). Due to these differences, results obtained by the mentioned methodologies might not be fully comparable.
- MeSH
- biotransformace MeSH
- časové faktory MeSH
- fenacetin metabolismus farmakologie MeSH
- játra účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- systém (enzymů) cytochromů P-450 chemie metabolismus MeSH
- tolbutamid metabolismus farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- aminopyrin škodlivé účinky terapeutické užití MeSH
- analgetika farmakologie chemie terapeutické užití MeSH
- Aspirin terapeutické užití MeSH
- chinin škodlivé účinky terapeutické užití MeSH
- fenacetin farmakologie škodlivé účinky terapeutické užití MeSH
- paracetamol farmakologie škodlivé účinky terapeutické užití MeSH
- MeSH
- ethanol farmakologie toxicita MeSH
- fenacetin analogy a deriváty farmakologie toxicita MeSH
- fyziologický stres MeSH
- imobilizace MeSH
- indomethacin farmakologie toxicita MeSH
- krysa rodu rattus MeSH
- žaludeční vředy chemicky indukované patologie prevence a kontrola MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
