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- W2037503886 abstract "A whole-body physiologically based pharmacokinetic (PBPK) model was developed for the prediction of unbound drug concentration-time profiles in the rat brain, in which drug transfer across the blood–brain barrier (BBB) was treated mechanistically by separating the parameters governing the rate (permeability) of BBB transfer from brain binding. An in vitro–in vivo scaling strategy based on Caco-2 cell permeability was proposed to extrapolate the active transporter-driven component of this permeability, in which a relative activity factor, RAF, was estimated by fitting the model to rat in vivo profiles. This scaling factor could be interpreted as the ratio of transporter activity between the in vitro system and the in vivo BBB, for a given drug in a given in vitro system. Morphine and oxycodone were selected to evaluate this strategy, as substrates of BBB-located efflux and influx transporters, respectively. After estimation of their respective RAFs using the rat model, the PBPK model was used to simulate human brain concentration profiles assuming the same RAF, and the implications of this were discussed. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:4277–4292, 2012" @default.
- W2037503886 created "2016-06-24" @default.
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- W2037503886 date "2012-11-01" @default.
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- W2037503886 title "Development of a Physiologically Based Pharmacokinetic Model for the Rat Central Nervous System and Determination of an In Vitro–In Vivo Scaling Methodology for the Blood–Brain Barrier Permeability of Two Transporter Substrates, Morphine and Oxycodone" @default.
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- W2037503886 doi "https://doi.org/10.1002/jps.23266" @default.
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