Adverse Drug-Drug Interaction Between Phenobarbital and Fluconazole in Two Dogs

Area of Science:

• Veterinary Pharmacology
• Drug Metabolism
• Canine Epilepsy

Background:

• Phenobarbital (PB) is a common antiseizure drug in dogs, metabolized by hepatic cytochrome P450 (CYP) enzymes.
• Fluconazole, an antifungal, inhibits CYP enzymes and may affect PB metabolism.
• Genetic variations, like CYP2C41 deletion, can influence drug interactions but are poorly understood in dogs.

Observation:

• Two epileptic dogs on chronic PB treatment experienced severe sedation and ataxia.
• These clinical signs coincided with increased serum PB concentrations after fluconazole administration.
• Both dogs were homozygous for a CYP2C41 gene deletion.

Findings:

• Fluconazole co-administration led to a significant increase in PB serum concentrations and toxicity in dogs.
• The observed drug interaction did not depend on the presence of CYP2C41 enzyme activity.
• Discontinuing fluconazole resolved the clinical signs and normalized PB levels.

Implications:

• Fluconazole can inhibit PB metabolism in dogs, causing potentially dangerous drug interactions.
• Monitoring PB concentrations is crucial when co-administering fluconazole to dogs.
• Further research into CYP enzyme roles in canine drug metabolism is needed to predict interactions.