Pharmacokinetic assessment of the marker active metabolites 4-methylamino-antipyrin and 4-acetylamino-antipyrine after intravenous and intramuscular injection of metamizole in healthy horses

Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine, and dogs. MT is rapidly hydrolyzed to the active primary metabolite 4-methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared to other minor metabolites. Among the others secondary metabolites also 4-aminoantipyrine (AA) results also active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after 25 mg/kg MT by intravenous (IV) and intramuscular (IM) administrations in healthy horses. Six healthy racehorses, aged 9 to 13 years and weighing 480 to 590 kg, were randomly allocated to two equal treatment groups according to a 2x2 crossover study. Blood was collected at predetermined times within 24 h and plasma was analysed by a validated HPLC UV method. No behavioural changes or alterations in health parameters were observed in the IV or IM groups of animals during or after (up to 7 days) the drug administration. Plasma concentrations of MAA after IV and IM administrations of MT were detectable from 5 min to 10 h in all the horses. Plasma concentrations of AA were detectable in the same range of time of that found for MAA, but in smaller amount. Maximum concentration (Cmax), time to maximum concentration (Tmax) and AUMC 0-last of MAA were statistically different between IV and IM group (P 0.01). The AUCIM/AUCIV ratio of MAA was 1.06. Differently, AUC 0-last of AA was statistically different between the groups (P 0.05) with a AUCIM/AUCIV ratio of 0.54. The present study showed that no relevant difference in the MAA plasma concentration was found after IM and IV administration of MT.