Pharmacotherapeutic monitoring of dipyrone in northeastern Brazilian donkeys (Equus asinus).

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.