![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
WM Pardridge, D Triguero, J Yang and PA Cancilla
Department of Medicine, University of California, Los Angeles School of Medicine.
Drug and solute transport through in vitro and in vivo models of the blood-brain barrier (BBB) were compared to provide a measure of how well the in vitro model predicted BBB permeability found in vivo. The in vitro model employed bovine brain capillary endothelial cells in either primary tissue culture or as a continuous line grown on Transwells and placed in side-by-side diffusion chambers. The in vivo model of BBB transport utilized an internal carotid artery perfusion/capillary depletion method in anesthetized rats. BBB permeability in vivo and in vitro was measured for 15 radiolabeled drugs and for L-[3H]dopa, D-[14C]glucose and [3H]albumin. [3H]- or [14C]sucrose was used in vivo as a blood volume reference. Lipid solubility of each drug was measured based on the 1-octanol/Ringer's partition coefficient. The morphology of the endothelial cell in primary tissue culture was spindle-shaped and the morphology of the endothelial cell in continuous culture was cuboid-shaped. The cuboidal morphology demonstrated a 2-fold greater resistance to solute transport and was used for the majority of the in vitro studies. Drug and solute permeability coefficients (Pe) ranged from 3.9 X 10(-3) to 2.5 X 10(-1) cm/min in vitro and from 1.0 X 10(-5) to 2.1 X 10(-2) cm/min in vivo. The In of the permeability.surface area product in vitro correlated with the In partition coefficient (r = 0.62, P less than .0125) and the In permeability.surface area product in vivo correlated with the In partition coefficient (r = 0.84, P less than .0005).(ABSTRACT TRUNCATED AT 250 WORDS)
This article has been cited by other articles:
|
|
 |
|
  S. G. Summerfield, K. Read, D. J. Begley, T. Obradovic, I. J. Hidalgo, S. Coggon, A. V. Lewis, R. A. Porter, and P. Jeffrey Central Nervous System Drug Disposition: The Relationship between in Situ Brain Permeability and Brain Free Fraction J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 205 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhang, C. S. W. Li, Y. Ye, K. Johnson, J. Poe, S. Johnson, W. Bobrowski, R. Garrido, and C. Madhu Porcine Brain Microvessel Endothelial Cells as an in Vitro Model to Predict in Vivo Blood-Brain Barrier Permeability Drug Metab. Dispos., November 1, 2006; 34(11): 1935 - 1943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. B. Sadowska, C. S. Patlak, K. H. Petersson, and B. S. Stonestreet Effects of Multiple Courses of Antenatal Corticosteroids on Blood-Brain Barrier Permeability in the Ovine Fetus Reproductive Sciences, May 1, 2006; 13(4): 248 - 255. [Abstract] [PDF]
|
|
|
|
|
|
V. Josserand, H. Pelerin, B. de Bruin, B. Jego, B. Kuhnast, F. Hinnen, F. Duconge, R. Boisgard, F. Beuvon, F. Chassoux, et al. Evaluation of Drug Penetration into the Brain: A Double Study by in Vivo Imaging with Positron Emission Tomography and Using an in Vitro Model of the Human Blood-Brain Barrier J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 79 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cisternino, C. Mercier, F. Bourasset, F. Roux, and J.-M. Scherrmann Expression, Up-Regulation, and Transport Activity of the Multidrug-Resistance Protein Abcg2 at the Mouse Blood-Brain Barrier Cancer Res., May 1, 2004; 64(9): 3296 - 3301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Takanaga, N. Tokuda, S. Ohtsuki, K.-i. Hosoya, and T. Terasaki ATA2 Is Predominantly Expressed as System A at the Blood-Brain Barrier and Acts as Brain-to-Blood Efflux Transport for L-Proline Mol. Pharmacol., June 1, 2002; 61(6): 1289 - 1296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Török, J. Huwyler, J. Drewe, H. Gutmann, and G. Fricker Transport of the beta -Lactam Antibiotic Benzylpenicillin and the Dipeptide Glycylsarcosine by Brain Capillary Endothelial Cells In Vitro Drug Metab. Dispos., November 1, 1998; 26(11): 1144 - 1148. [Abstract] [Full Text]
|
|
|
|
|
|
C. Chen and G. M. Pollack Altered Disposition and Antinociception of [D-Penicillamine2,5] Enkephalin in mdr1a-Gene-Deficient Mice J. Pharmacol. Exp. Ther., November 1, 1998; 287(2): 545 - 552. [Abstract] [Full Text]
|
|
|
|
|
|
T. Kitazawa, T. Terasaki, H. Suzuki, A. Kakee, and Y. Sugiyama Efflux of Taurocholic Acid Across the Blood-Brain Barrier: Interaction with Cyclic Peptides J. Pharmacol. Exp. Ther., August 1, 1998; 286(2): 890 - 895. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Duport, F. Robert, D. Muller, G. Grau, L. Parisi, and L. Stoppini An in vitro blood-brain barrier model: Cocultures between endothelial cells and organotypic brain slice cultures PNAS, February 17, 1998; 95(4): 1840 - 1845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chen and G. M. Pollack Blood-Brain Disposition and Antinociceptive Effects of [D-Penicillamine2,5]enkephalin in the Mouse J. Pharmacol. Exp. Ther., December 1, 1997; 283(3): 1151 - 1159. [Abstract] [Full Text]
|
|
|
|
|
|
T. Ooie, T. Terasaki, H. Suzuki, and Y. Sugiyama Quantitative Brain Microdialysis Study on the Mechanism of Quinolones Distribution in the Central Nervous System Drug Metab. Dispos., July 1, 1997; 25(7): 784 - 789. [Abstract] [Full Text]
|
|
|
|
|
|
S. A. Thomas, T. J. Abbruscato, V. S. Hau, T. J. Gillespie, J. Zsigo, V. J. Hruby, and T. P. Davis Structure-Activity Relationships of a Series of [D-Ala2]Deltorphin I and II Analogues; in Vitro Blood-Brain Barrier Permeability and Stability J. Pharmacol. Exp. Ther., May 1, 1997; 281(2): 817 - 825. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
