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Acetaminophen pharmacokinetics in geese

Irene SartiniDepartment of Veterinary Medicine, University of Sassari, Sassari, Italy

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Beata Łebkowska-WieruszewskaDepartment of Pharmacology, Toxicology and Environmental Protection, University of Life Sciences, Lublin, Poland

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Małgorzata Gbylik-SikorskaDepartment of Pharmacology and Toxicology, National Veterinary Research Institute, Puławy, Poland

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Konrad PietrukDepartment of Pharmacology and Toxicology, National Veterinary Research Institute, Puławy, Poland

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Aleksandra KrawczykDepartment of Animal Anatomy and Histology, University of Life Sciences, Lublin, Poland

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Anna GajdaDepartment of Pharmacology and Toxicology, National Veterinary Research Institute, Puławy, Poland

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Andrzej LisowskiInstitute of Animal Breeding and Biodiversity Conservation, University of Life Sciences, Lublin, Poland

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Amnart PoapolathepDepartment of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, Thailand

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Mario GiorgiDepartment of Veterinary Sciences, University of Pisa, Pisa, Italy
School of veterinary Sciences, Department of Veterinary Medicine, University of Sassari, Sassari, Italy

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Abstract

OBJECTIVE

To evaluate the pharmacokinetics of acetaminophen (APAP) after single-dose IV and PO in the goose; to quantify APAP and its main metabolites in goose muscle, heart, lung, liver, and kidney; and to perform a histopathologic evaluation of goose stomach, duodenum, liver, and kidney tissues for potential signs of toxicity.

ANIMALS

24 geese.

PROCEDURES

Geese were randomly divided into 3 groups (n = 8). Group I received APAP (10 mg/kg) IV, and groups II and III received the same dose PO. Groups I and II were used for the pharmacokinetic assessment, and group III was used for the residue analysis and histopathologic evaluation. APAP and its metabolites were quantified in plasma and tissues by ultra–high-performance liquid chromatography–tandem mass spectrometry, and the pharmacokinetic analysis was performed using a noncompartmental approach.

RESULTS

APAP plasma concentrations were lower than those of the metabolites in similar selected time points after both treatments. After IV treatment, the APAP area under the curve value was statistically higher than that after PO administration, resulting in an oral bioavailability of 46%. In contrast, the area under the curve of the metabolites following PO administration was statistically higher than those found after IV administration. Tissue residues of APAP were highest in the liver, with an accumulation index > 1. Fatty degeneration of hepatocytes was observed 24 hours after administration of APAP.

CLINICAL RELEVANCE

In geese, treatment by PO administration of APAP shows incomplete absorption and a slight accumulation in lung and liver. Tissue alterations occurred in the liver at 24 hours, while no signs of toxicity were found in the other tested organs.

Abstract

OBJECTIVE

To evaluate the pharmacokinetics of acetaminophen (APAP) after single-dose IV and PO in the goose; to quantify APAP and its main metabolites in goose muscle, heart, lung, liver, and kidney; and to perform a histopathologic evaluation of goose stomach, duodenum, liver, and kidney tissues for potential signs of toxicity.

ANIMALS

24 geese.

PROCEDURES

Geese were randomly divided into 3 groups (n = 8). Group I received APAP (10 mg/kg) IV, and groups II and III received the same dose PO. Groups I and II were used for the pharmacokinetic assessment, and group III was used for the residue analysis and histopathologic evaluation. APAP and its metabolites were quantified in plasma and tissues by ultra–high-performance liquid chromatography–tandem mass spectrometry, and the pharmacokinetic analysis was performed using a noncompartmental approach.

RESULTS

APAP plasma concentrations were lower than those of the metabolites in similar selected time points after both treatments. After IV treatment, the APAP area under the curve value was statistically higher than that after PO administration, resulting in an oral bioavailability of 46%. In contrast, the area under the curve of the metabolites following PO administration was statistically higher than those found after IV administration. Tissue residues of APAP were highest in the liver, with an accumulation index > 1. Fatty degeneration of hepatocytes was observed 24 hours after administration of APAP.

CLINICAL RELEVANCE

In geese, treatment by PO administration of APAP shows incomplete absorption and a slight accumulation in lung and liver. Tissue alterations occurred in the liver at 24 hours, while no signs of toxicity were found in the other tested organs.

Contributor Notes

Corresponding author: Dr. Giorgi (mario.giorgi@unipi.it)