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

Marie-Pierre Dehouck 1 Pascale Jolliet-Riant Françoise Brée Jean-Charles Fruchart Roméo Cecchelli 1 Jean-Paul Tillement 2
1 LBHE - Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique
2 Laboratoire de Pharmacologie
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.
Keywords : Drug transport Blood-brain barrier Brain extraction In vitro coculture Brain capillary endothelial cells Astrocytes Centrally acting drug screening In vivo intracarotid injection
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Journal articles
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Submitted on : Tuesday, October 26, 2010 - 12:47:13 PM
Last modification on : Wednesday, September 4, 2019 - 1:52:11 PM

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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, Wiley, 1992, 58 (5), p. 1790-1797. ⟨hal-00529693⟩

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