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

Authors
Lee, Soo HyunAn, Ji HyeLee, Hwa JeongJung, Byung Hwa
Issue Date
2012-09
Publisher
WILEY-BLACKWELL
Citation
BIOPHARMACEUTICS & DRUG DISPOSITION, v.33, no.6, pp.292 - 303
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; AUCmetabolite/AUCAPAP) were also observed to evaluate the change of APAP metabolism. The AUCs of APAP and APAP-Glth (glutathione) were higher and the AUCAPAP-Sul/AUCAPAP (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 (c) 2012 John Wiley & Sons, Ltd.
Keywords
CONTAINING AMINO-ACIDS; 3-PHOSPHOADENOSINE 5-PHOSPHOSULFATE; GASTROINTESTINAL-TRACT; INTESTINAL MICROFLORA; PLASMA PROFILES; PARACETAMOL; METABOLISM; SULFATE; ABSORPTION; BIOAVAILABILITY; CONTAINING AMINO-ACIDS; 3-PHOSPHOADENOSINE 5-PHOSPHOSULFATE; GASTROINTESTINAL-TRACT; INTESTINAL MICROFLORA; PLASMA PROFILES; PARACETAMOL; METABOLISM; SULFATE; ABSORPTION; BIOAVAILABILITY; gut microflora; pseudo germ-free rats; acetaminophen; LC-MS; MS; metabolism; pharmacokinetics
ISSN
0142-2782
URI
https://pubs.kist.re.kr/handle/201004/128942
DOI
10.1002/bdd.1799
Appears in Collections:
KIST Article > 2012
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE