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Entry of diazepam and its major metabolite into cerebrospinal fluid
- Source :
- Psychopharmacology. 70:89-93
- Publication Year :
- 1980
- Publisher :
- Springer Science and Business Media LLC, 1980.
-
Abstract
- Five dogs received a single 1.0 mg/kg dose of diazepam (DZ) IV. Concentrations of DZ and its major metabolite desmethyldiazepam (DMDZ) were simultaneously measured in plasma and cisternal cerebrospinal fluid (CSF) for up to 8 h after the dose by electron-capture gas-liquid chromatography. DZ was rapidly eliminated from plasma (half-life 0.3--1.3 h); DZ disappearance was mirrored by formation of DMDZ, which in turn was eliminated slowly, Both DZ and DMDZ rapidly penetrated CSF and concentrations in CSF declined parallel with those in plasma. Despite rapid uptake, the extent of CSF transfer of DZ and DMDZ was limited by plasma protein binding. Mean CSF:plasma concentrtion ratios for DZ (range 0.023--0.137) and DMDZ (range 0.047--0.119) were highly correlated with the unbound fraction in plasma (r = 0.95 and 0.80, respectively). Thus DZ and DMDZ concentrations in CSF, presumed to reflect concentrations at the site of action, are determined by unbound plasma concentrations. The intensity of pharmacologic action is more likely to correlate with unbound than with total plasma concentrations.
- Subjects :
- Pharmacology
medicine.medical_specialty
Diazepam
Total plasma
Metabolite
Nordazepam
Blood Proteins
Plasma protein binding
Blood–brain barrier
Pharmacologic action
chemistry.chemical_compound
Dogs
Endocrinology
Cerebrospinal fluid
medicine.anatomical_structure
chemistry
Internal medicine
Anesthesia
medicine
Animals
Site of action
Protein Binding
medicine.drug
Subjects
Details
- ISSN :
- 14322072 and 00333158
- Volume :
- 70
- Database :
- OpenAIRE
- Journal :
- Psychopharmacology
- Accession number :
- edsair.doi.dedup.....692cb202c13fae8614f7b812e2f76c5a