ArticlePharmaceutical research1991
Assessment of drug disposition in the perfused rat brain by statistical moment analysis.
Article in Pharmaceutical research, 1991. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
- Cytochrome P450-mediated drug metabolism in the brain.Journal of psychiatry & neuroscience : JPN · 2013Review
- An isolated in-situ rat head perfusion model for pharmacokinetic studies.Pharmaceutical research · 2000Article
- Pharmacokinetic considerations of regional administration and drug targeting: influence of site of input in target tissue and flux of binding protein.Journal of pharmacokinetics and biopharmaceutics · 1996Article
- Discrepancies in pharmacokinetic parameter estimation between bolus and infusion studies in the perfused rat hindlimb.Journal of pharmacokinetics and biopharmaceutics · 1995Article
- Physiological pharmacokinetics of solutes in the isolated perfused rat hindlimb: characterization of the physiology with changing perfusate flow, protein content, and temperature using statistical moment analysis.Journal of pharmacokinetics and biopharmaceutics · 1993Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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