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  • Title: Ampicillin and an ester in experimental Hemophilus influenzae meningitis.
    Author: Bodine JA, Strausbaugh LJ, Sande MA.
    Journal: Clin Pharmacol Ther; 1976 Dec; 20(6):727-32. PubMed ID: 1086758.
    Abstract:
    A new methoxymethyl ester of hetacillin is highly lipid-soluble, a property which was expected to enhance its penetration into the central nervous system (CNS). We compared the penetration of the ester and ampicillin into the cerebrospinal fluid (CSF) of normal rabbits and those with experimental Hemophilus influenzae meningitis. In normal rabbits treated by constant intravenous infusion, mean per cent penetration (see article) of the ester was four times as great as that of ampicillin (6.6 +/- 3.7% against 1.6 +/- 1.9%), and the difference in CSF drug levels attained was accentuated when bolus IV infusion was used. Drug concentration in brain tissue was three times as great in a rabbit treated with the ester (0.79 mug/gm against 0.26 mug/gm). In rabbits with meningitis, the ester again achieved higher CSF concentrations. Per cent penetration into CSF in infected rabbits was 23% for the ester and 13% for ampicillin. Bactericidal activity of the drugs was comparable; over 8 hr of treatment both drugs significantly reduced the CSF bacterial titers of infected animals. Our data demonstrated that the ester enters the CSF and CNS in higher concentration than ampicillin, with no loss in bactericidal activity.
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