Breed-Specific Differences in Firocoxib Pharmacokinetics and Hepatorenal Safety: Enhanced Systemic Exposure in Beagles Versus Native Egyptian Dogs

Abstract Purpose: The present study aimed to investigate the pharmacokinetics and short-term safety profile of Firocoxib, a selective COX-2 inhibitor, in Beagle dogs compared to Egyptian native dogs. The main research question was whether breed and body weight differences influence drug absorption, distribution, and safety parameters following oral administration. Methods: A single oral dose of Firocoxib (5 mg/kg) was administered to healthy Beagle and Egyptian native dogs (n = X per group). Blood samples were collected at multiple time points up to 24 hours post-dosing. Plasma drug concentrations were quantified using validated HPLC methods, and pharmacokinetic parameters (Cmax, Tmax, AUC0–24, t1/2) were calculated via non-compartmental analysis. Liver function biomarkers (ALT, AST) were measured to assess short-term hepatic safety. Statistical comparisons between breeds were performed using independent t-tests with significance set at p < 0.05. Results: Firocoxib was well tolerated in both breeds, with no adverse clinical signs observed. Egyptian native dogs exhibited significantly higher Cmax and AUC0–24 values compared to Beagles, while Tmax and t1/2 showed no notable differences. Plasma concentration-time curves indicated faster and greater drug exposure in native dogs. Correlation analysis revealed a positive association between body weight and drug plasma levels at 6 hours. Liver enzyme activities (ALT, AST) remained within normal ranges across both groups. Conclusion: Breed-specific differences influence Firocoxib pharmacokinetics, with Egyptian native dogs showing enhanced drug exposure compared to Beagles. These findings highlight the need for considering breed and body weight in optimizing veterinary pharmacotherapy and ensuring effective and safe NSAID use. Trial Registration: This experimental animal study was not prospectively registered, as trial registration is not applicable for veterinary pharmacokinetic studies. Ethical approval was obtained from the Institutional Animal Care and Use Committee (IACUC No. VET2025/AMLO/021, approval date: March 2025).