RESUMO
Metamizole (MT), also known as dipyrone, is an analgesic and antipyretic drug labeled for use in humans and domestic animals in some countries. As with other drugs, the administration of MT in donkeys is based on studies carried out with horses. In the present report, we aimed to determine the pharmacokinetics of the two main metamizole active metabolites (N-methyl-4-aminoantipyrine [MAA] and 4-aminoantipyrine [AA]) following 10 (M10 ) and 25 mg/kg (M25 ) IV metamizole doses in Northeast Brazilian donkeys (n = 10). Blood was collected at predetermined times within over 48 h; MAA and AA plasma concentrations were determined by a validated LC-MS/MS method. The metabolites were quantifiable in the M10 until 12 h and M25 until 24 h after drug administration. As expected, AUC0ât , AUC0â∞, and Cmax demonstrated significant differences increases in metamizole metabolites profiles when groups were compared. No adverse effects were observed. This study indicates the need for an extremely sensitive analytical method to adequately characterize the pharmacokinetics of active metabolites of MT, MAA, and AA. In conclusion, the method developed in this research was able to measure the active metabolites of metamizole and with that it was possible to establish their pharmacokinetic profile. Furthermore, after projection of the minimum MAA concentrations, it is possible to infer that the dose of 10 mg/kg will be used on donkeys at 6 h intervals, while the M25 group at 12 h intervals. However, clinical studies are needed to assess this hypothesis.
