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

Journal Article · Sat Jul 01 04:00:00 EDT 1989 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:5813725

Nohjoh, T; Suzuki, H; Sawada, Y; Sugiyama, Y; Iga, T; Hanano, M

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.

• Research Organization: Univ. of Tokyo (Japan)
• OSTI ID: 5813725
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 250:1; ISSN JPETA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
AROMATICS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY TEMPERATURE
CARBON ISOTOPES
DRUGS
HYDROXY COMPOUNDS
HYPOTHERMIA
INHIBITION
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE TRANSPORT
METABOLISM
NITRO COMPOUNDS
NITROPHENOL
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHENOLS
RATS
REACTION KINETICS
REAGENTS
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES