Jaramillo Maria, Mondino Alejandra, Court Michael, Lewis Melissa J, Olby Natasha J, Muñana Karen R
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
Comparative Pharmacogenomics Laboratory, Program in Individualized Medicine, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
J Vet Intern Med. 2025 Jul-Aug;39(4):e70190. doi: 10.1111/jvim.70190.
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.
苯巴比妥（PB）是一种广泛用于犬类的抗癫痫药物，由肝脏细胞色素P450（CYP）酶代谢。氟康唑是一种常用的抗真菌药物，可抑制多种CYP同工酶，并可能损害PB的代谢。尽管在犬类中尚未得到充分表征，但CYP2C41基因缺失等基因多态性可改变CYP活性并影响药物相互作用。我们描述了两只接受慢性PB治疗的癫痫犬，在接受氟康唑后出现明显的镇静和共济失调，血清PB浓度升高。两只犬均为CYP2C41缺失的纯合子。停用氟康唑导致PB浓度降低和临床症状缓解。这些发现表明氟康唑可抑制PB代谢，导致具有临床相关性的毒性，并且这种相互作用不需要CYP2C41酶的表达。建议在联合使用氟康唑期间监测PB浓度。需要进一步表征CYP酶在犬类PB代谢中的作用，以更好地预测药物相互作用。
