Pharmacokinetic profiles of the two major active metabolites of metamizole, 4-methylaminoantipyrine (MAA) and 4-aminoantipyrine (AA), after intravenous injection in cats

Res Vet Sci. 2023 Feb;155:156-160. doi: 10.1016/j.rvsc.2023.01.007. Epub 2023 Jan 18.

Abstract

This study aimed to determine the pharmacokinetic profile of two active metabolites of metamizole (dipyrone), N-methyl-4-aminoanthypyrine (MAA) and 4-aminoanthypyrine (AA), after intravenous administration in cats. Eight healthy mixed-breed cats were intravenously administered metamizole (25 mg/kg). Blood samples were collected at predetermined time points for up to 48 h after administration. Information on behavioral changes in the animals and adverse effects was collected. Plasma aliquots were processed and analyzed using the ultra-performance liquid chromatography tandem mass spectrometry technique. A validated UPLC-MS/MS method was used to characterize the pharmacokinetics of MAA and AA. Salivation was identified as an adverse clinical sign. The mean maximal plasma concentrations of MAA and AA were 29.31 ± 24.57 μg/mL and 1.69 ± 0.36 μg/mL, with half-lives of around 4.98 and 14 h, respectively. The area under the plasma concentration curve values were 28.54 ± 11.33 and 49.54 ± 11.38 h*μg/mL for MAA and AA, respectively. The plasma concentration of MAA was detectable for up to 24 h and was smaller than AA. AA was detectable for >48 h. Results suggest that metamizole is converted into active metabolites in cats. Further PK/PD and safety studies should be performed before defining the dose or administration intervals for clinical use.

Keywords: 4-aminoantipyrine; Analgesics; Dipyrone; Feline; N-methyl-4-aminoantipyrine.

MeSH terms

  • Ampyrone* / chemistry
  • Ampyrone* / pharmacokinetics
  • Animals
  • Cats
  • Chromatography, Liquid / veterinary
  • Dipyrone* / pharmacokinetics
  • Injections, Intravenous / veterinary
  • Tandem Mass Spectrometry / veterinary

Substances

  • noramidopyrine
  • Dipyrone
  • Ampyrone