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Published on: January 2, 2017

A study of cephalothin and desacetylcephalothin in cerebrospinal fluid in therapy for experimental pneumococcal

C M Nolan, W C Ulmer

    The Journal of Infectious Diseases
    |March 1, 1980
    PubMed

    Insights

    Cephalothin

    Area of Science:

    • Pharmacology
    • Infectious Diseases
    • Neuroscience

    Background:

    • Cephalothin is a cephalosporin antibiotic.
    • Bacterial meningitis is a serious infection of the membranes surrounding the brain and spinal cord.
    • The efficacy of cephalothin in treating bacterial meningitis is suboptimal.

    Purpose of the Study:

    • To investigate the pharmacokinetic properties of cephalothin and its metabolite, desacetylcephalothin, in the cerebrospinal fluid (CSF) during experimental pneumococcal meningitis.
    • To determine the role of the choroid plexus in the transport and metabolism of cephalothin.

    Main Methods:

    • Experimental pneumococcal meningitis was induced in rabbits.
    • Intramuscular injections of cephalothin were administered.
    • CSF and serum levels of cephalothin and desacetylcephalothin were measured.
    • In vitro studies using isolated choroid plexuses were performed to assess drug uptake and metabolism.

    Main Results:

    • Desacetylcephalothin, a less active metabolite, achieved higher peak levels and had a longer half-life in the CSF compared to cephalothin.
    • The choroid plexus demonstrated greater uptake of cephalothin than desacetylcephalothin in vitro.
    • Direct metabolism of cephalothin to desacetylcephalothin by the choroid plexus was observed.

    Conclusions:

    • Intrathecal metabolism of cephalothin by the choroid plexus may contribute to its reduced efficacy in treating bacterial meningitis.
    • The accumulation of the less active metabolite, desacetylcephalothin, in the CSF could impair treatment outcomes.

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