Document Detail


Intestinal clearance of H2-antagonists.
MedLine Citation:
PMID:  7914403     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Jejunal perfusion of cimetidine resulted in the appearance of lumenal cimetidine sulfoxide in both rats and humans. In the rat, ileal perfusion yielded negligible sulfoxide metabolite as compared with that of the jejunum. Jejunal co-perfusion of an anionic-exchange inhibitor, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, blocked the appearance of drug sulfoxide, and methionine co-perfusion yielded concentration-dependent inhibition of lumenal cimetidine sulfoxide. Intravenous injection of high concentrations of cimetidine sulfoxide did not produce detectable lumenal metabolite levels during jejunal perfusion of drug-free buffer, providing in situ evidence that lumenal metabolite is generated by the small intestine. The extent of the appearance of lumenal sulfoxide was significantly greater for cimetidine than for the other three marketed H2-antagonists in rat jejunum. Variable intestinal clearance of this extensively prescribed class of therapeutic agents may contribute to their absorption variability.
Authors:
Y F Hui; J Kolars; Z Hu; D Fleisher
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  48     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1994 Jul 
Date Detail:
Created Date:  1994-09-06     Completed Date:  1994-09-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  229-31     Citation Subset:  IM    
Affiliation:
College of Pharmacy, University of Michigan, Ann Arbor 48109.
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MeSH Terms
Descriptor/Qualifier:
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / administration & dosage
Animals
Cimetidine / analogs & derivatives,  analysis,  pharmacokinetics
Famotidine / pharmacokinetics
Histamine H2 Antagonists / pharmacokinetics*
Humans
Intestinal Mucosa / metabolism*
Jejunum / metabolism*
Methionine / administration & dosage
Perfusion
Rats
Chemical
Reg. No./Substance:
0/Histamine H2 Antagonists; 51481-61-9/Cimetidine; 53005-05-3/4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; 54237-72-8/cimetidine sulfoxide; 63-68-3/Methionine; 76824-35-6/Famotidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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