Pharmacokinetics of dipyrone in horses: A multi-dose, dose escalation study

Dipyrone is a non-opioid, nonsteroidal anti-inflammatory drug with antipyretic and analgesic properties commonly used in horses. Dipyrone is rapidly hydrolyzed to the primary active metabolite 4-methylaminoantipyrine (4-MAA). The purpose of this study was to determine the pharmacokinetic profile of 4-MAA following repeated and escalating doses of intravenously administered dipyrone. Twenty-six horses were randomly allocated to five treatment groups (one placebo group and four dipyrone groups [30 mg/kg q8h, 30 mg/kg q12h, 60 mg/kg q8h, and 90 mg/kg q12h]) and treated for nine consecutive days. Blood was collected at predetermined timepoints, and plasma was analyzed for 4-MAA concentrations with a validated LC/MS/MS method. Following a single dose, there was a linear correlation to the maximum concentration (C-max) achieved. There was a disproportionate increase in the minimum concentration (C-min) of 4-MAA with accumulation occurring at higher doses or more frequent dosing intervals. Significant differences were noted in 4-MAA C-max, half-life, and area under the curve during the dosing interval (AUC(tau)) when dipyrone was administered at 30 mg/kg q12h versus q8h. Adverse effects attributed to drug administration were not noted.