Comparative pharmacokinetics of caffeine and three metabolites in clinically normal horses and donkeys

Abstract

Objective - To determine whether clearance of capacitylimited drugs in horses differs from that in donkeys by comparing the serum disposition of caffeine and its metabolites, theophylline, theobromine, and paraxanthine after IV administration of caffeine to horses and donkeys. Animals - 4 healthy horses and 5 healthy donkeys. Procedure - Blood samples were collected from each animal at time 0 (before) and 5, 10, 15, 20, 30, and 45 minutes, and 1, 2, 3, 4, 6, 8, 12, 24, 30, 36, 48, 54, 60, 72, and 96 hours after IV administration of a bolus of caffeine. Serum was analyzed in triplicate by high-performance liquid chromatography to determine caffeine, theophylline, theobromine, and paraxanthine concentrations. The serum concentration-time curves for each animal were analyzed separately to estimate model-independent pharmacokinetic variables. Results - Mean pharmacokinetic values for caffeine, theophylline, and paraxanthine did not differ significantly in horses, compared with donkeys. Mean peak serum concentration of theobromine was significantly higher in donkeys, compared with horses. Conclusion - Clearance of the capacity-limited drug caffeine does net appear to differ in horses, compared with donkeys. Clinical Relevance - For some drugs that undergo hepatic metabolism, the dose and dose interval used for horses may be appropriate for use in donkeys.