ABSTRACT
This study aimed to monitor the effects of dipyrone following multiple administrations in northeastern donkeys. Ten castrated male donkeys, aged 6.4 ± 3 years and weighing 130.6 ± 9.8 kg, were administered dipyrone (25 mg/kg IV) every 12 h, resulting in six administrations (D1 to D6) per animal. Blood samples were collected over a 72 h monitoring period. A validated UHPLC-MS/MS method was employed to determine the plasma concentrations of the 4- methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA). The calculated pharmacokinetic variables of 4-MAA after D1 and D6 were, respectively: Cmax (µg/mL) = 163.60 ± 179.72 and 178.79 ± 196.94; T1/2beta (h) = 2.65 ± 0.65 and 3.37 ± 1.03; and AUC0-t (µg/mL × h) = 240.38 ± 130.87 and 373.52 ± 78.85. The same variables for 4-AA were: Cmax, (µg/mL) = 0.44 ± 0.27 and 0.90 ± 0.31, T1/2beta (h) = 14.77 ± 13.13 and 35.97 and AUC0-t (µg/mL × h) = 3.20 ± 0.43 and 27.73 ± 11.99. Concentrations of 4-MAA exceeded the minimum concentration required for 50% inhibition of cyclooxygenases 1 and 2. However, an accumulation of 4-AA, was observed. Further clinical studies are necessary to ascertain the implications of these findings on the pharmacodynamic response to dipyrone in northeastern donkeys.
