Cerebrospinal fluid uptake and peripheral distribution of centrally acting drugs: Relation to lipid solubility

Hermann R. Ochs, David J. Greenblatt, Darrell R. Abernethy, Rainer M. ARENDT, Joachim Gerloff, Wolfgang Eichelkraut, Norbert Hahn

Research output: Contribution to journalArticle

Abstract

In an anaesthetized dog model, serum kinetics and CSF entry were determined after i.v. administration of the following 8 drugs: salicylic acid (as acetylsalicylic acid), antipyrine, acetaminophen (paracetamol), lidocaine (lignocaine), trimipramine, amitriptyline, haloperidol, and imipramine. Kinetic variables were evaluated in relation to in‐vitro lipophilicity, measured by the reverse‐phase high‐pressure liquid chromatographic (HPLC) retention index. After correction for individual values of serum binding (determined as the CSF: serum ratio at equilibrium), in‐vivo volume of distribution was highly correlated with HPLC retention (r = 0.92). Conversely, the time of peak CSF concentration and the CSF entry half‐life were negatively correlated with HPLC retention (r = −0.83 and −0.63, respectively). Thus lipophilicity is a physiochemical property which has an influence on the peripheral distribution of drugs as well as their rate of entry into CSF. 1985 Royal Pharmaceutical Society of Great Britain

Original languageEnglish (US)
Pages (from-to)428-431
Number of pages4
JournalJournal of Pharmacy and Pharmacology
Volume37
Issue number6
DOIs
StatePublished - Jun 1985

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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    Ochs, H. R., Greenblatt, D. J., Abernethy, D. R., ARENDT, R. M., Gerloff, J., Eichelkraut, W., & Hahn, N. (1985). Cerebrospinal fluid uptake and peripheral distribution of centrally acting drugs: Relation to lipid solubility. Journal of Pharmacy and Pharmacology, 37(6), 428-431. https://doi.org/10.1111/j.2042-7158.1985.tb03030.x