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Cerebrospinal fluid uptake and peripheral distribution of centrally acting drugs: Relation to lipid solubility
- Source :
- Journal of Pharmacy and Pharmacology. 37:428-431
- Publication Year :
- 1985
- Publisher :
- Oxford University Press (OUP), 1985.
-
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.
- Subjects :
- Pharmacology
Volume of distribution
Chromatography
Chemistry
Pharmaceutical Science
Trimipramine
Lipids
High-performance liquid chromatography
Imipramine
Kinetics
Dogs
Cerebrospinal fluid
Pharmaceutical Preparations
Solubility
Lipophilicity
medicine
Animals
Kovats retention index
Distribution (pharmacology)
Half-Life
medicine.drug
Subjects
Details
- ISSN :
- 20427158 and 00223573
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Journal of Pharmacy and Pharmacology
- Accession number :
- edsair.doi.dedup.....0c039a61cb448d1f74b3ad5a9816761e