Adverse Drug–Drug Interaction Between Phenobarbital and Fluconazole in Two Dogs
ABSTRACT Phenobarbital (PB) is an antiseizure medication widely used in dogs that is metabolized by hepatic cytochrome P450 (CYP) enzymes. Fluconazole, a commonly prescribed antifungal medication, inhibits several CYP isoenzymes and can impair PB metabolism. Genetic polymorphisms such as the CYP2C41...
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| Format: | Article |
| Language: | English |
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Wiley
2025-07-01
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| Series: | Journal of Veterinary Internal Medicine |
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| Online Access: | https://doi.org/10.1111/jvim.70190 |
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| _version_ | 1849254025934929920 |
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| author | Maria Jaramillo Alejandra Mondino Michael Court Melissa J. Lewis Natasha J. Olby Karen R. Muñana |
| author_facet | Maria Jaramillo Alejandra Mondino Michael Court Melissa J. Lewis Natasha J. Olby Karen R. Muñana |
| author_sort | Maria Jaramillo |
| collection | DOAJ |
| description | ABSTRACT Phenobarbital (PB) is an antiseizure medication widely used in dogs that is metabolized by hepatic cytochrome P450 (CYP) enzymes. Fluconazole, a commonly prescribed antifungal medication, inhibits several CYP isoenzymes and can impair PB metabolism. Genetic polymorphisms such as the CYP2C41 gene deletion can alter CYP activity and influence drug interactions, although not well characterized in dogs. We describe two epileptic dogs on chronic PB treatment that developed marked sedation and ataxia, and increased serum PB concentrations after receiving fluconazole. Both dogs were homozygous for the CYP2C41 deletion. Discontinuation of fluconazole resulted in decreased PB concentrations and resolution of clinical signs. These findings suggest fluconazole can inhibit PB metabolism, leading to clinically relevant toxicity, and this interaction does not require CYP2C41 enzyme expression. Monitoring PB concentrations during fluconazole co‐administration is advised. Further characterization of the role of CYP enzymes in PB metabolism in dogs is needed to better predict drug interactions. |
| format | Article |
| id | doaj-art-9e1df5966f4149678a97c41e09004074 |
| institution | Kabale University |
| issn | 0891-6640 1939-1676 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Veterinary Internal Medicine |
| spelling | doaj-art-9e1df5966f4149678a97c41e090040742025-08-20T03:56:09ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762025-07-01394n/an/a10.1111/jvim.70190Adverse Drug–Drug Interaction Between Phenobarbital and Fluconazole in Two DogsMaria Jaramillo0Alejandra Mondino1Michael Court2Melissa J. Lewis3Natasha J. Olby4Karen R. Muñana5Department of Clinical Sciences, College of Veterinary Medicine North Carolina State University Raleigh North Carolina USADepartment of Clinical Sciences, College of Veterinary Medicine North Carolina State University Raleigh North Carolina USAComparative Pharmacogenomics Laboratory, Program in Individualized Medicine, Department of Veterinary Clinical Sciences, College of Veterinary Medicine Washington State University Pullman Washington USADepartment of Clinical Sciences, College of Veterinary Medicine North Carolina State University Raleigh North Carolina USADepartment of Clinical Sciences, College of Veterinary Medicine North Carolina State University Raleigh North Carolina USADepartment of Clinical Sciences, College of Veterinary Medicine North Carolina State University Raleigh North Carolina USAABSTRACT Phenobarbital (PB) is an antiseizure medication widely used in dogs that is metabolized by hepatic cytochrome P450 (CYP) enzymes. Fluconazole, a commonly prescribed antifungal medication, inhibits several CYP isoenzymes and can impair PB metabolism. Genetic polymorphisms such as the CYP2C41 gene deletion can alter CYP activity and influence drug interactions, although not well characterized in dogs. We describe two epileptic dogs on chronic PB treatment that developed marked sedation and ataxia, and increased serum PB concentrations after receiving fluconazole. Both dogs were homozygous for the CYP2C41 deletion. Discontinuation of fluconazole resulted in decreased PB concentrations and resolution of clinical signs. These findings suggest fluconazole can inhibit PB metabolism, leading to clinically relevant toxicity, and this interaction does not require CYP2C41 enzyme expression. Monitoring PB concentrations during fluconazole co‐administration is advised. Further characterization of the role of CYP enzymes in PB metabolism in dogs is needed to better predict drug interactions.https://doi.org/10.1111/jvim.70190antiseizure medicationcanineCYP2C41cytochrome P450epilepsyhepatotoxicity |
| spellingShingle | Maria Jaramillo Alejandra Mondino Michael Court Melissa J. Lewis Natasha J. Olby Karen R. Muñana Adverse Drug–Drug Interaction Between Phenobarbital and Fluconazole in Two Dogs Journal of Veterinary Internal Medicine antiseizure medication canine CYP2C41 cytochrome P450 epilepsy hepatotoxicity |
| title | Adverse Drug–Drug Interaction Between Phenobarbital and Fluconazole in Two Dogs |
| title_full | Adverse Drug–Drug Interaction Between Phenobarbital and Fluconazole in Two Dogs |
| title_fullStr | Adverse Drug–Drug Interaction Between Phenobarbital and Fluconazole in Two Dogs |
| title_full_unstemmed | Adverse Drug–Drug Interaction Between Phenobarbital and Fluconazole in Two Dogs |
| title_short | Adverse Drug–Drug Interaction Between Phenobarbital and Fluconazole in Two Dogs |
| title_sort | adverse drug drug interaction between phenobarbital and fluconazole in two dogs |
| topic | antiseizure medication canine CYP2C41 cytochrome P450 epilepsy hepatotoxicity |
| url | https://doi.org/10.1111/jvim.70190 |
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