Pharmacokinetic Assessment of the Marker Active Metabolites 4-Methyl-amino-antipyrine and 4-Acetyl-amino-antipyrine After Intravenous and Intramuscular Injection of Metamizole (Dipyrone) in Healthy Donkeys

Pharmacokinetic profiles of the two major active metabolites of metamizole (dipyrone) in cats following three different routes of administration

“…A relatively similar AUC EV/i.v . ratio was found in a recent study in the dog (Giorgi et al., submitted), which used the same injection site, buttock muscle, as the present study, whereas, horses, sheep, and donkeys were injected in the neck muscle (Aupanun et al., ; Giorgi et al., , ). In general, the extent of systemic absorption of drugs injected intramuscularly is higher when the site of injection is the lateral neck compared to the buttock region, as this location provides a larger absorptive surface area with higher blood flow to tissues (Baggot, ).…”

“…The i.m.‐administered group showed the shortest elimination half‐life among the routes of administration. The present study showed markedly longer elimination half‐life in all administration routes than those previously reported for humans (4–5.5 hr), horses (4.2–6.4 hr), and donkeys (2.6–3.8 hr) with higher C max and AUC values (Aupanun et al., ; Giorgi et al., ; Vlahov et al., ). AA is known to be converted into AAA by a polymorphic N‐acetyltransferase (NAT2) enzyme (Geisslinger, Böcker, & Levy, ).…”

“…The elimination rate constant of MAA was similar in all administration routes with an elimination half‐life of about 6–7 hr, which was evidently longer than those from the sheep, horse, and donkey (about 1–3 hr) (Aupanun et al., ; Giorgi et al., , ). This might suggest relatively slow elimination of MAA itself or conversion of MAA to AA in cats.…”

“…ratio (1.06 and 1.12 for horse and sheep, respectively) (Giorgi et al., , ). Moreover, in donkeys, the AUC was even higher in the i.m.‐administered group when compared to the i.v.‐treated group with statistical significance (Aupanun et al., ). In the present study, cats showed a relatively low AUC EV/i.v .…”

“…and i.m. administrations in sheep, horses, and donkeys (Aupanun et al., ; Giorgi et al., , ). However, unlike the present study, the AUC values were comparable between i.v.‐ and i.m.‐administered groups in horses and sheep, indicating similar drug exposure in the body after both injectable administrations with high AUC EV/i.v .…”