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Abstract

H+ coupled transport of p.o. cephalosporins via dipeptide carriers in rabbit intestinal brush-border membranes: difference of transport characteristics between cefixime and cephradine.

K Inui, T Okano, H Maegawa, M Kato, M Takano and R Hori
Journal of Pharmacology and Experimental Therapeutics October 1988, 247 (1) 235-241;
K Inui
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T Okano
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H Maegawa
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M Kato
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M Takano
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R Hori
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Abstract

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).

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Journal of Pharmacology and Experimental Therapeutics
Vol. 247, Issue 1
1 Oct 1988
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Abstract

H+ coupled transport of p.o. cephalosporins via dipeptide carriers in rabbit intestinal brush-border membranes: difference of transport characteristics between cefixime and cephradine.

K Inui, T Okano, H Maegawa, M Kato, M Takano and R Hori
Journal of Pharmacology and Experimental Therapeutics October 1, 1988, 247 (1) 235-241;

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Abstract

H+ coupled transport of p.o. cephalosporins via dipeptide carriers in rabbit intestinal brush-border membranes: difference of transport characteristics between cefixime and cephradine.

K Inui, T Okano, H Maegawa, M Kato, M Takano and R Hori
Journal of Pharmacology and Experimental Therapeutics October 1, 1988, 247 (1) 235-241;
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