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Clinical Pharmacokinetics of Cerebrospinal Fluid

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Summary

The distribution of drugs into the cerebrospinal fluid has long been considered a challenging field of investigation in 2 major respects: (a) understanding how the physicochemical properties (molecular weight, pKa, plasma protein binding) of various molecules influence their movements across such a specific structure as the blood-brain barrier; and (b) defining the relationship between cerebrospinal fluid concentrations of various drugs and their central (side) effects. An attempt has been made to review the very dispersed information presently available to offer a clinically orientated picture of this area of pharmacokinetics. Drugs acting on the central nervous system (benzodiazepines, tricyclic antidepressants, anticonvulsants, opioids), antibacterial agents, cardiovascular drugs (β-adrenoceptor blockers and digoxin), antineoplastic drugs (mainly methotrexate), and other miscellaneous agents (corticosteroids, cimetidine, methylxanthines) are reviewed.

The available evidence seems to support the conclusion that only for methotrexate and antibacterial agents does knowledge of cerebrospinal fluid pharmacokinetics have direct therapeutic implications, while the mosaic of information available for other drugs does little more than provide a partially satisfactory picture.

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  1. Laboratory of Clinical Pharmacology, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milan, Italy

    Maurizio Bonati, Jussi Kanto & Gianni Tognoni

  2. Leiras Pharmaceutical Plant, Turku, Finland

    Maurizio Bonati, Jussi Kanto & Gianni Tognoni

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Bonati, M., Kanto, J. & Tognoni, G. Clinical Pharmacokinetics of Cerebrospinal Fluid. Clin Pharmacokinet 7, 312–335 (1982). https://doi.org/10.2165/00003088-198207040-00003

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