Assessment of drug disposition in the perfused rat brain by statistical moment analysis
- Faculty of Pharmaceutical Sciences, Setsunan University, Osaka (Japan)
Drug disposition in the brain was investigated by statistical moment analysis using an improved in situ brain perfusion technique. The right cerebral hemisphere of the rat was perfused in situ. The drug and inulin were injected into the right internal carotid artery as a rapid bolus and the venous outflow curve at the posterior facial vein was obtained. The infusion rate was adjusted to minimize the flow of perfusion fluid into the left hemisphere. The obtained disposition parameters were characteristics and considered to reflect the physicochemical properties of each drug. Antipyrine showed a small degree of initial uptake. Therefore, its apparent distribution volume (Vi) and apparent intrinsic clearance (CLint,i) were small. Diazepam showed large degrees of both influx and efflux and, thus, a large Vi. Water showed parameters intermediate between those of antipyrine and those of diazepam. Imipramine, desipramine, and propranolol showed a large CLint,i compared with those of the other drugs. The extraction ratio of propranolol significantly decreased with increasing concentrations of unlabeled propranolol in the perfusion fluid. These findings may be explained partly by the tissue binding of these drugs. In conclusion, the present method is useful for studying drug disposition in the brain.
- OSTI ID:
- 5393082
- Journal Information:
- Pharmaceutical Research; (United States), Vol. 8:6; ISSN 0724-8741
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BLOOD-BRAIN BARRIER
PERMEABILITY
DRUGS
TISSUE DISTRIBUTION
ANTIPYRINE
BIOLOGICAL AVAILABILITY
BRAIN
CARBON ISOTOPES
INULIN
METABOLISM
PERFUSED ORGANS
PHARMACOLOGY
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
ANTIPYRETICS
AZOLES
BODY
CARBOHYDRATES
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DISTRIBUTION
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
POLYSACCHARIDES
PYRAZOLES
PYRAZOLINES
RODENTS
SACCHARIDES
VERTEBRATES
550501* - Metabolism- Tracer Techniques