Document Detail


H+ coupled transport of p.o. cephalosporins via dipeptide carriers in rabbit intestinal brush-border membranes: difference of transport characteristics between cefixime and cephradine.
MedLine Citation:
PMID:  3171973     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We demonstrated previously that aminocephalosporins, such as cephradine, possessing a alpha-amino group and a carboxyl group, are transported via H+/dipeptide carrier system in the intestinal brush-border membranes. The present study examined the transport characteristics of cefixime, a new p.o. cephalosporin with two carboxyl groups, by the rabbit intestinal brush-border membrane vesicles in comparison with those of cephradine. With an intravesicular pH of 7.5, apparent optimum extravesicular pH was 6.0 for cephradine uptake and more acidic (pH 4.5-5.0) for cefixime uptake. An inward H+ gradient [( pH]i = 7.5, [pH]o = 5.0) induced overshoot uptake of cefixime, and this uptake was reduced in the presence of carbonyl cyanide p-trifluoromethoxyphenylhydrazone, a protonophore. Cefixime uptake at pH 5.0 was trans-stimulated (countertransport effect) and cis-inhibited by dipeptides and aminocephalosporins but not at pH 7.5. Cephradine uptake at pH 7.5 was stimulated by the countertransport effect of dipeptide but not by cefixime. Cefixime and cephradine uptake at pH 5.0 was greatly inhibited by 4,4'-diisothiocyano-2,2'-disulfonic stilbene. These findings indicate that cefixime is transported by an inward H+ gradient via dipeptide carrier only in an acidic pH region, whereas cephradine is transported via dipeptide carrier in both neutral and acidic pH regions, suggesting the existence of multiple transport systems for dipeptides; a neutral pH preferring system (Type I) and an acidic pH preferring system (Type II).
Authors:
K Inui; T Okano; H Maegawa; M Kato; M Takano; R Hori
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  247     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1988 Oct 
Date Detail:
Created Date:  1988-11-18     Completed Date:  1988-11-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  235-41     Citation Subset:  IM    
Affiliation:
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Japan.
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MeSH Terms
Descriptor/Qualifier:
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / analogs & derivatives,  pharmacology
Administration, Oral
Animals
Biological Transport
Cefixime
Cefotaxime / analogs & derivatives*,  pharmacokinetics
Cephalosporins / pharmacokinetics*
Cephradine / pharmacokinetics*
Dipeptides / pharmacokinetics*
Hydrogen-Ion Concentration
Intestines / metabolism*
Male
Microvilli / metabolism
Rabbits
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Cephalosporins; 0/Dipeptides; 27816-59-7/4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 38821-53-3/Cephradine; 53005-05-3/4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; 63527-52-6/Cefotaxime; 79350-37-1/Cefixime

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


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