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Journal Articles Journal of Neurochemistry Year : 1992

Drug transfer across the blood-brain barrier: correlation between in vitro and in vivo models

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Abstract

To assess the drug transport across the blood-brain barrier (BBB), we compared the maximal brain extraction values at time 0 [E(O) values] obtained using either in vitro or in vivo methods. The in vitro BBB model consisted of a coculture of brain capillary endothelial cells growing on one side of a filter and astrocytes on the other. The in vivo model used intracarotid injection in anesthetized rats. Eleven compounds were tested. They were selected because they exhibit quantitatively different brain extraction rates: very low for inulin and sucrose, low for oxicam-related nonsteroidal antiinflammatory drugs and diclofenac, and high for propranolol and diazepam. As these compounds are apparently transferred by a passive diffusion mechanism, two others, glucose and leucine, were added that cross the BBB by a known carrier-mediated process. The in vivo and in vitro E(0) values showed a strong correlation as indicated by the Spearman's correlation coefficient (r = 0.88, p < 0.01). The relative ease with which such cocultures can be produced in large quantities could facilitate the screening of new centrally acting drugs.
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hal-00529693 , version 1 (26-10-2010)

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  • HAL Id : hal-00529693 , version 1

Cite

Marie-Pierre Dehouck, Pascale Jolliet-Riant, Françoise Brée, Jean-Charles Fruchart, Roméo Cecchelli, et al.. Drug transfer across the blood-brain barrier: correlation between in vitro and in vivo models. Journal of Neurochemistry, 1992, 58 (5), p. 1790-1797. ⟨hal-00529693⟩
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