The difference of acetaminophen metabolism in normal and pseudo germ-free rats

Title
The difference of acetaminophen metabolism in normal and pseudo germ-free rats
Authors
안지혜정봉철이화정정병화
Issue Date
2011-04
Publisher
The second Korea Metabolomics Society Symposium
Abstract
Investigation on the function of intestinal micro gut-flora to drug metabolism is important since intestinal microorganisms are capable of a variety of actions during the metabolism of drugs, especially in de-conjugation of substances in the small intestine. For this purpose, the acetaminophen (APAP) which has diverse phase 1 and phase 2 metabolites was selected as the test drug, and the metabolism and pharmacokinetics (PK) were examined in normal and pseudo germ-free rats (male SD rat, 7-8 week of age). Pseudo germ-free rats were made by oral administration of neomycin, bacitracin and streptomycin twice a day at the dose of 200mg/kg each for five days. Control rats were made by oral administration water instead of antibiotics. After 2 days of withdrawal time, the pseudo germ-free group and the control group were administered 200mg/kg of APAP orally. Plasma was collected following the time schedules and it was analyzed by LC-MS/MS. The PK parameter of APAP and its metabolites was calculated by non-compartment model on WinNonlin program. Clearance, half-life, volume of distribution were not significantly different between the two groups. But, the area under the plasma concentration-time curve (AUC) of APAP and acetaminophen glutathione (APAP-Glth) in the pseudo germ-free group was significantly higher than the control group (P<0.05). To estimate the metabolic change, we calculated the AUCconjugation metabolites/AUCAPAP. In results, AUCAPAP-Sulfate/AUCAPAP decreased significantly in pseudo germ-free group than the control group (p<0.01). The results indicated that APAP metabolism could be changed by the condition of intestinal micro gut-flora. Therefore, the effect of intestinal micro gut-flora should be considered in the drug treatments.
URI
http://pubs.kist.re.kr/handle/201004/39666
Appears in Collections:
KIST Publication > Conference Paper
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