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Journal of veterinary pharmacology and therapeutics2021; 44(5); 842-849; doi: 10.1111/jvp.12998

Pharmacokinetic properties of metamizole active metabolites in Northeastern Brazilian donkeys (Equus asinus).

Abstract: 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 (M ) and 25 mg/kg (M ) 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 M until 12 h and M until 24 h after drug administration. As expected, AUC , AUC and C 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.
© 2021 John Wiley & Sons Ltd.
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Publication Date: 2021-07-15 PubMed ID: 34268764DOI: 10.1111/jvp.12998Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article reports on a study aimed at determining the pharmacokinetics of the two main active metabolites of the drug Metamizole in Northeast Brazilian donkeys. The study concluded that an extremely sensitive analytical method is needed to adequately characterize these pharmacokinetics, and clinical studies may be necessary to confirm their application intervals.

Research Context and Objectives

  • The study was conducted in response to the fact that the use of the drug Metamizole (MT), an analgesic and antipyretic drug, in donkeys is based on studies performed on horses, not specifically on donkeys.
  • The researchers aimed to assess the pharmacokinetics of the two main active metabolites of Metamizole, N-methyl-4-aminoantipyrine (MAA) and 4-aminoantipyrine (AA), in Northeast Brazilian donkeys. Pharmacokinetics refers to how the body affects a specific drug after administration.

Research Methodology

  • Two different intravenous doses of Metamizole—10mg/kg and 25mg/kg—were administered to the donkeys (n=10).
  • Blood samples were then collected at predetermined times up to 48 hours after the administration of the drug.
  • The concentrations of MAA and AA in the plasma were determined using a validated LC-MS/MS method, a highly sensitive and specific analytical technique used for quantifying molecules in complex samples.
  • The metabolites were monitored up to 12 hours for the 10mg group and 24 hours for the 25mg group following drug administration.

Results and Observations

  • The researchers noted significant differences and increases in the profiles of the Metamizole metabolites when comparing the two groups.
  • No adverse effects were observed during the study.
  • The authors suggested that due to the intricate behavior of the metabolites, a highly sensitive analytical method is required to adequately characterize the pharmacokinetics of MAA and AA.

Conclusions and Future Research

  • The study successfully established the pharmacokinetic profile of the active metabolites of Metamizole in donkeys, offering a basis for further research and application.
  • The projected minimum concentrations of MAA suggest that a dose of 10mg/kg can potentially be used on donkeys at 6-hour intervals, while a dose of 25mg/kg can be used at 12-hour intervals. These predictions, however, need to be confirmed through clinical studies.

Cite This Article

APA
de Macêdo LB, Mouta AN, Araújo-Silva G, Urizar JTP, de Paula VV. (2021). Pharmacokinetic properties of metamizole active metabolites in Northeastern Brazilian donkeys (Equus asinus). J Vet Pharmacol Ther, 44(5), 842-849. https://doi.org/10.1111/jvp.12998

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 44
Issue: 5
Pages: 842-849

Researcher Affiliations

de Macêdo, Luã B
  • Universidade Federal Rural do Semi Árido, Mossoró, RN, Brazil.
Mouta, Andressa N
  • Universidade Federal Rural do Semi Árido, Mossoró, RN, Brazil.
Araújo-Silva, Gabriel
  • Universidade do Estado do Amapá, Macapá, AP, Brazil.
Urizar, Jose Trinidad P
  • Universidad Autónoma de San Luis Potosí, San Luis Potosí - SLP, Mexico.
de Paula, Valéria V
  • Universidade Federal Rural do Semi Árido, Mossoró, RN, Brazil.

MeSH Terms

  • Ampyrone
  • Animals
  • Chromatography, Liquid / veterinary
  • Dipyrone
  • Equidae
  • Tandem Mass Spectrometry / veterinary

Grant Funding

  • Coordenau00e7u00e3o de Aperfeiu00e7oamento de Pessoal de Nu00edvel Superior

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Citations

This article has been cited 2 times.
  1. Mouta AN, Arcoverde KN, Fernandes NS, Passos YDB, Oliveira CVA, Honorato RA, Araujo-Silva G, Paula VV. Pharmacokinetic Profile of Two Active Dipyrone Metabolites, 4-Methylaminoantipyrine (MAA) and 4-Aminoantipyrine (AA), Following Intravenous Administration in Dogs: A Preliminary Study. Animals (Basel) 2025 Jun 5;15(11).
    doi: 10.3390/ani15111666pubmed: 40509132google scholar: lookup
  2. Araújo-Silva G, de Macêdo LB, Mouta AN, de Oliveira MGC, Arcoverde KN, Solon LGS, Perez-Urizar JT, de Paula VV. Tramadol and M1 Bioavailability Induced by Metamizole Co-Administration in Donkeys (Equus asinus). Animals (Basel) 2024 Mar 17;14(6).
    doi: 10.3390/ani14060929pubmed: 38540027google scholar: lookup
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