ArticlePharmaceutical research2011
A new in situ brain perfusion flow correction method for lipophilic drugs based on the pH-dependent Crone-Renkin equation.
Article in Pharmaceutical research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 27 citations in OpenAlex.
- Brain endothelial permeability, transport, and flow assessed over 10 orders of magnitude using the in situ brain perfusion technique.Fluids and barriers of the CNS · 2024Article
- Article
- Understanding the brain uptake and permeability of small molecules through the BBB: A technical overview.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Review
- Article
- Closed-Loop Doluisio (Colon, Small Intestine) and Single-Pass Intestinal Perfusion (Colon, Jejunum) in Rat-Biophysical Model and Predictions Based on Caco-2.Pharmaceutical research · 2017Article
- Revisiting atenolol as a low passive permeability marker.Fluids and barriers of the CNS · 2017Article
- Challenges of using in vitro data for modeling P-glycoprotein efflux in the blood-brain barrier.Pharmaceutical research · 2014Review
- In vitro, in vivo and in silico models of drug distribution into the brain.Journal of pharmacokinetics and pharmacodynamics · 2013Review
- Biorelevant pK(a) (37 °C) predicted from the 2D structure of the molecule and its pK(a) at 25 °C.Journal of pharmaceutical and biomedical analysis · 2011Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo determine the flow-corrected luminal permeability, P(c), of lipophilic drugs measured by the in situ brain perfusion method under circumstances where the traditional Crone-Renkin equation (CRE) method, using diazepam as a flow marker, often fails.
methodsThe pH-dependent rate of brain penetration of five lipophilic drugs (amitriptyline, atomoxetine, imipramine, indomethacin, maprotiline, sertraline), as well as of atenolol and antipyrine, were measured in Sprague-Dawley rats. A new pH-dependent CRE was derived and applied to remove the hydrodynamic component of effective permeability, P(e), to produce P(c) values.
resultsIt was shown by the analysis of the in situ data in the pH 6.5-8.5 interval for the lipophilic bases that the average vascular flow F(pf) = 0.036 mL∙g(-1)∙s(-1), centered in a "flow-limit window" (FLW) bounded by P (e) (min) = 170 and P (e) (max) = 776 (10(-6) cm∙s(-1) units). It was shown that the traditional CRE is expected not to work for half of the molecules in the FLW and is expected to underestimate (up to 64-fold) the other half of the molecules.
conclusionThe new pH-CRE flow correction method applied to lipophilic ionizable drugs, based on the pH partition hypothesis, can overcome the limitations of the traditional CRE.
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