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AN EFFECT OF PHENOBARBITONE ON GRISEOFULVIN METABOLISM IN THE RAT.
British Journal of Pharmacology and Chemotherapy
|February 1, 1964
Summary
Phenobarbitone significantly reduces griseofulvin blood levels in rats by increasing its metabolism. This effect, observed in both sexes, lasts for days and is more pronounced with repeated phenobarbitone doses.
Area of Science:
- Pharmacology and Toxicology
- Drug Metabolism Studies
Background:
- Griseofulvin is an antifungal medication used to treat various skin infections.
- Phenobarbitone is a barbiturate with known effects on drug metabolism.
Purpose of the Study:
- To investigate the effect of phenobarbitone pretreatment on griseofulvin blood levels and metabolism in rats.
- To determine the duration and intensity of phenobarbitone's impact on griseofulvin pharmacokinetics.
Main Methods:
- Rats (male and female) were administered phenobarbitone prior to oral or intravenous griseofulvin dosing.
- Blood levels of griseofulvin were monitored over time.
- In vitro metabolism of griseofulvin by liver slices from treated and untreated rats was assessed.
Main Results:
- Phenobarbitone administration led to a significant decrease in griseofulvin blood levels.
- The reduction in griseofulvin levels was observed as early as 12 hours, peaking between 12-48 hours, and persisting for at least 96 hours.
- Repeated phenobarbitone dosing resulted in a more pronounced effect.
- Liver slices from phenobarbitone-treated rats exhibited more rapid griseofulvin metabolism.
Conclusions:
- Phenobarbitone enhances the metabolism of griseofulvin, leading to lower circulating levels of the antifungal drug.
- These findings suggest potential drug interactions that may impact the clinical efficacy of griseofulvin.
- Further research is warranted to explore the clinical implications for patients receiving both medications.