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  • Title: Facilitated transport of cefodizime into the rat central nervous system.
    Author: Matsushita H, Suzuki H, Sugiyama Y, Sawada Y, Iga T, Kawaguchi Y, Hanano M.
    Journal: J Pharmacol Exp Ther; 1991 Nov; 259(2):620-5. PubMed ID: 1941610.
    Abstract:
    The disposition of [14C]cefodizime, a nonmetabolizable analog of cefotaxime, in the central nervous system was studied in control and benzylpenicillin-infused rats using in vivo experimental techniques. After i.v. bolus administration of [14C]cefodizime, a concentration gradient was established from the brain extracellular fluid (ECF) to the cerebrospinal fluid (CSF) (i.e., drug penetration into the CSF after i.v. administration can be accounted for by permeation across the cerebral capillaries and diffusion through the brain ECF and across the ependymal surface into the CSF). Kinetic analysis indicated that the cerebrovascular transfer coefficient for plasma unbound [14C]cefodizime in control rats equaled 5.2 x 10(-5) ml/sec/g brain, a value comparable to that for mannitol. In rats which received an i.v. infusion of benzylpenicillin, the cerebrovascular transfer coefficient for [14C]cefodizime was reduced to approximately 1/15th of the control value, resulting in a reduced central nervous system (brain ECF and CSF)/plasma unbound concentration ratio for this drug. After i.c.v. administration, the efflux of [14C]cefodizime from CSF was comparable to that of [3H]mannitol with a small probenecid-sensitive component and was not affected by treatment with benzylpenicillin. These results indicate that the unidirectional influx of [14C]cefodizime into brain ECF and then into the CSF is facilitated by a mechanism shared with other beta-lactam antibiotics.
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