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J Vet Pharmacol Ther. 2018 Jun;41(3):428-436. doi: 10.1111/jvp.12484. Epub 2018 Jan 19.

Pharmacokinetic profiles of the active metamizole metabolites after four different routes of administration in healthy dogs.

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Department of Veterinary Sciences, University of Pisa, Pisa, Italy.
Department of Pharmacology, University of Life Sciences, Lublin, Poland.
Department of Animal Hygiene and Environment, University of Life Sciences, Lublin, Poland.
Department of Veterinary Sciences, University of Queensland, Gatton, Australia.
Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, Thailand.
College of Veterinary Medicine, Chungnam National University, Daejeon, South Korea.
Department of Veterinary Medicine, University of Sassari, Sassari, Italy.


Metamizole (MT), an analgesic and antipyretic drug, is rapidly hydrolyzed to the active primary metabolite 4-methylaminoantipyrine (MAA) and relatively active secondary metabolite 4-aminoantipyrine (AA). The aim of this study was to assess the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.), intramuscular (i.m.), oral (p.o.), and rectal (RC) routes in dogs. Six dogs were randomly allocated to an open, single-dose, four-treatment, four-phase, unpaired, crossover study design. Blood was collected at predetermined times within 24 hr, and plasma was analyzed by a validated HPLC-UV method. Plasma concentrations of MAA and AA after i.v., i.m., p.o., and RC administrations of MT were detectable from 5 (i.v. and i.m.) or 30 (p.o. and RC) min to 24 hr in all dogs. The highest concentrations of MAA were found in the i.v., then i.m., p.o., and RC groups. Plasma concentrations of AA were similar for i.v., i.m., and RC, and the concentrations were approximately double those in the PO groups. The AUCEV/IV ratio for MAA was 0.75 ± 0.11, 0.59 ± 0.08, and 0.32 ± 0.05, for i.m., p.o., and RC, respectively. The AUCEV/IV ratio for AA was 1.21 ± 0.33, 2.17 ± 0.62, and 1.08 ± 0.19, for i.m., p.o., and RC, respectively. Although further studies are needed, rectal administration seems to be the least suitable route of administration for MT in the dog.


analgesic; dipyrone; dog; metabolism; pharmacokinetics

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