Transport of cefodizime, a novel third generation cephalosporin antibiotic, in isolated rat choroid plexus
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), Vol. 250:1
- Country of Publication:
- United States
- Language:
- English
Similar Records
Cotransport of sodium and chloride by the adult mammalian choroid plexus
Increased {beta}-amyloid levels in the choroid plexus following lead exposure and the involvement of low-density lipoprotein receptor protein-1
Related Subjects
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