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Evaluation of pharmacokinetic differences of acetaminophen in pseudo germ-free rats

Title
Evaluation of pharmacokinetic differences of acetaminophen in pseudo germ-free rats
Authors
Lee S.H.An J.H.Lee H.J.Jung B.H.
Ewha Authors
이화정
SCOPUS Author ID
이화정scopus
Issue Date
2012
Journal Title
Biopharmaceutics and Drug Disposition
ISSN
0142-2782JCR Link
Citation
vol. 33, no. 6, pp. 292 - 303
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
To evaluate the metabolic interaction between host and gut microflora on drug metabolism, pseudo germ-free rats were prepared with an antibiotics cocktail to change their gut conditions. The usefulness of the pseudo germ-free model was evaluated for observing the DMPK of acetaminophen (APAP). Pseudo germ-free rats were prepared by orally administering antibiotic cocktails consisting of bacitracin, streptomycin and neomycin, and then APAP was orally administered to control and pseudo germ-free rats. The plasma concentration of APAP and its six metabolites were quantified using a validated LC-MS/MS method. A non-compartment model estimated the pharmacokinetic parameters of APAP and its metabolites, and the ratios of the area under curve (AUC; AUC metabolite/AUC APAP) were also observed to evaluate the change of APAP metabolism. The AUCs of APAP and APAP-Glth (glutathione) were higher and the AUC APAP-Sul/AUC APAP (metabolic efficiency of sulfate conjugation) was lower in pseudo germ-free rats than those in the control rats. The decrease in metabolic efficiency of sulphate conjugation could result from the reduction of the sulphate supply, causing an increase of the AUC of APAP and APAP-Glth. The activities of gut microflora can affect the state of hepatic sulphate for drug conjugation, indirectly leading to characteristic APAP metabolism. These results indicate that gut microflora may play an important role in the pharmacokinetics and metabolism of APAP. Thus, the metabolic interaction between host and gut microflora should be considered upon drug administration and pseudo germ-free rats prepared in the present study can be competent for investigating the metabolic interaction between host and gut microflora on drug metabolism. Copyright © 2012 John Wiley & Sons, Ltd.
DOI
10.1002/bdd.1799
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약학대학 > 약학과 > Journal papers
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