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Title: Transport of cefodizime, a novel third generation cephalosporin antibiotic, in isolated rat choroid plexus

Abstract

To characterize the transport system by which cephalosporin antibiotics are accumulated by the choroid plexus, kinetic analysis of cefodizime transport was performed. Accumulation of cefodizime was against an electrochemical potential gradient via a saturable process (Km = 470 microM, Vmax = 174 nmol/ml of tissue per min) that was inhibited by metabolic inhibitors (KCN and 2,4-dinitrophenol), hypothermia, a sulfhydryl reagent (p-hydroxymer-curibenzoic acid) and anion transport inhibitors (probenecid and 4,4'-diisothiocyanostilbene -2,2'-disulfonic acid). Accumulation of cefodizime was inhibited competitively by benzylpenicillin with an inhibition constant of aproximately 100 microM. Cefodizime inhibited competitively the accumulation of benzylpenicillin with an inhibition constant of approximately 500 microM. Kinetic analysis using 16 kinds of beta-lactam antibiotics also supported the view (1) that the transport system of cefodizime is shared by benzylpenicillin and (2) that these beta-lactam antibiotics are transported via a common transport system. These findings indicate that the major transport system of cephalosporin antibiotics in the rat choroid plexus is via a carrier-mediated active anion transport process. The affinity of beta-lactam antibiotics for this transport system in the choroid plexus may be a major factor in determining their pharmacokinetics in the cerebrospinal fluid.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Univ. of Tokyo (Japan)
OSTI Identifier:
5813725
Resource Type:
Journal Article
Journal Name:
J. Pharmacol. Exp. Ther.; (United States)
Additional Journal Information:
Journal Volume: 250:1
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; ANTIBIOTICS; MEMBRANE TRANSPORT; NITROPHENOL; BIOLOGICAL EFFECTS; BIOCHEMICAL REACTION KINETICS; CARBON ISOTOPES; HYPOTHERMIA; INHIBITION; METABOLISM; RATS; REAGENTS; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ANIMALS; ANTI-INFECTIVE AGENTS; AROMATICS; BODY TEMPERATURE; DRUGS; HYDROXY COMPOUNDS; ISOTOPE APPLICATIONS; ISOTOPES; KINETICS; LABELLED COMPOUNDS; MAMMALS; NITRO COMPOUNDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PHENOLS; REACTION KINETICS; RODENTS; VERTEBRATES; 560300* - Chemicals Metabolism & Toxicology; 550501 - Metabolism- Tracer Techniques

Citation Formats

Nohjoh, T, Suzuki, H, Sawada, Y, Sugiyama, Y, Iga, T, and Hanano, M. Transport of cefodizime, a novel third generation cephalosporin antibiotic, in isolated rat choroid plexus. United States: N. p., 1989. Web.
Nohjoh, T, Suzuki, H, Sawada, Y, Sugiyama, Y, Iga, T, & Hanano, M. Transport of cefodizime, a novel third generation cephalosporin antibiotic, in isolated rat choroid plexus. United States.
Nohjoh, T, Suzuki, H, Sawada, Y, Sugiyama, Y, Iga, T, and Hanano, M. 1989. "Transport of cefodizime, a novel third generation cephalosporin antibiotic, in isolated rat choroid plexus". United States.
@article{osti_5813725,
title = {Transport of cefodizime, a novel third generation cephalosporin antibiotic, in isolated rat choroid plexus},
author = {Nohjoh, T and Suzuki, H and Sawada, Y and Sugiyama, Y and Iga, T and Hanano, M},
abstractNote = {To characterize the transport system by which cephalosporin antibiotics are accumulated by the choroid plexus, kinetic analysis of cefodizime transport was performed. Accumulation of cefodizime was against an electrochemical potential gradient via a saturable process (Km = 470 microM, Vmax = 174 nmol/ml of tissue per min) that was inhibited by metabolic inhibitors (KCN and 2,4-dinitrophenol), hypothermia, a sulfhydryl reagent (p-hydroxymer-curibenzoic acid) and anion transport inhibitors (probenecid and 4,4'-diisothiocyanostilbene -2,2'-disulfonic acid). Accumulation of cefodizime was inhibited competitively by benzylpenicillin with an inhibition constant of aproximately 100 microM. Cefodizime inhibited competitively the accumulation of benzylpenicillin with an inhibition constant of approximately 500 microM. Kinetic analysis using 16 kinds of beta-lactam antibiotics also supported the view (1) that the transport system of cefodizime is shared by benzylpenicillin and (2) that these beta-lactam antibiotics are transported via a common transport system. These findings indicate that the major transport system of cephalosporin antibiotics in the rat choroid plexus is via a carrier-mediated active anion transport process. The affinity of beta-lactam antibiotics for this transport system in the choroid plexus may be a major factor in determining their pharmacokinetics in the cerebrospinal fluid.},
doi = {},
url = {https://www.osti.gov/biblio/5813725}, journal = {J. Pharmacol. Exp. Ther.; (United States)},
number = ,
volume = 250:1,
place = {United States},
year = {Sat Jul 01 00:00:00 EDT 1989},
month = {Sat Jul 01 00:00:00 EDT 1989}
}