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Research in veterinary science2010; 89(1); 113-119; doi: 10.1016/j.rvsc.2010.02.002

Species comparison of oral bioavailability, first-pass metabolism and pharmacokinetics of acetaminophen.

Abstract: Species differences in oral bioavailability, first-pass metabolism and pharmacokinetics of biopharmaceutics classification system (BCS) class I compound acetaminophen were studied. The absolute bioavailability was 42.2%, 39.0%, 44.5%, 75.5% and 91.0% in chickens, turkeys, dogs, pigs and horses, respectively. After hydrolysis of metabolites by beta-glucuronidase/sulfatase, apparent bioavailability increased significantly in all species (turkeys: 72.4%, dogs: 100.5%, pigs: 102.2%), except horses (91.6%). Mean metabolic ratios of [acetaminophen glucuronide]/[acetaminophen] between 0 and 1h were significantly higher after oral dosing in turkeys, dogs and pigs, revealing the role of first-pass metabolism in incomplete bioavailability. Evidence of species differences in acetaminophen metabolism is provided by differences in plasma clearance, which was inversely proportional to bioavailability. In conclusion, differences in BA appeared to originate predominantly from differences in first-pass metabolism, demonstrating that the BCS high permeability classification of acetaminophen is consistent across the mammalian species studied. In turkeys, however, incomplete absorption additionally seemed to contribute to the low BA.
Copyright 2010 Elsevier Ltd. All rights reserved.
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Publication Date: 2010-03-07 PubMed ID: 20211479DOI: 10.1016/j.rvsc.2010.02.002Google Scholar: Lookup
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  • Comparative Study
  • Journal Article

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 investigated the differences in how various species absorb, metabolize, and excrete acetaminophen, a common pain reliever. It found that absorption and metabolism rates of acetaminophen varied among chickens, turkeys, dogs, pigs, and horses, with chickens and turkeys showing the lowest absorption rates, while horses, pigs, and dogs exhibited higher absorption.

Methodology and Findings

  • The research used a biopharmaceutics classification system (BCS) class I compound (acetaminophen) to study species differences in oral bioavailability, first-pass metabolism, and pharmacokinetics.
  • Absolute bioavailability, or the rate and extent a drug becomes available to the target tissue after administration, varied among the species studied. Chickens and turkeys had the lowest rates (42.2% and 39.0%, respectively), dogs and pigs had higher rates (44.5% and 75.5%, respectively), and horses had the highest rate (91.0%).
  • After hydrolysis of acetaminophen metabolites by beta-glucuronidase/sulfatase, an enzyme that breaks down complex molecules, the apparent bioavailability increased significantly in all species, with the exception of horses.
  • The mean metabolic ratios of acetaminophen glucuronide to acetaminophen were significantly higher after oral dosing in turkeys, dogs, and pigs, indicating that first-pass metabolism played a significant role in these species’ incomplete bioavailability of acetaminophen. Horses maintained the highest rate of bioavailability.

Conclusions

  • The study concluded that differences in bioavailability among the species could be attributed mainly to differences in first-pass metabolism. This suggests that acetaminophen’s designation as a BCS high permeability compound is consistent across the mammalian species studied.
  • In the case of turkeys, additional factors, such as incomplete absorption of the drug, seemed to contribute to their particularly low bioavailability.
  • Differences in plasma clearance, or the rate at which a drug is removed from the bloodstream, inversely correlated with bioavailability. This means that species with higher bioavailability had slower plasma clearance rates and vice versa.

Cite This Article

APA
Neirinckx E, Vervaet C, De Boever S, Remon JP, Gommeren K, Daminet S, De Backer P, Croubels S. (2010). Species comparison of oral bioavailability, first-pass metabolism and pharmacokinetics of acetaminophen. Res Vet Sci, 89(1), 113-119. https://doi.org/10.1016/j.rvsc.2010.02.002

Publication

Research in veterinary science
ISSN: 1532-2661
NlmUniqueID: 0401300
Country: England
Language: English
Volume: 89
Issue: 1
Pages: 113-119

Researcher Affiliations

Neirinckx, E
  • Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. eva.neirinckx@ugent.be
Vervaet, C
    De Boever, S
      Remon, J P
        Gommeren, K
          Daminet, S
            De Backer, P
              Croubels, S

                MeSH Terms

                • Acetaminophen / administration & dosage
                • Acetaminophen / pharmacokinetics
                • Administration, Oral
                • Analgesics / administration & dosage
                • Analgesics / pharmacokinetics
                • Animals
                • Animals, Domestic / metabolism
                • Biological Availability
                • Chickens / metabolism
                • Cross-Over Studies
                • Dogs / metabolism
                • Female
                • Horses / metabolism
                • Male
                • Poultry / metabolism
                • Species Specificity
                • Swine / metabolism
                • Turkeys / metabolism

                Citations

                This article has been cited 13 times.
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