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in-ADME Research Copyright © 2012
in-ADME ResearchpCEL-X Rev 4.0
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Presentation Copyrighted (C) 2012. in-ADME Research. All rights reserved.
(b) SNAPSHOT PREVIEW OF PASSIVE PERMEABILITY (37oC)Caco-2 at pH 5.0, 6.5, and 7.4 Human Intestinal Permeability (based on Lennernäs-Amidon Peff data)
(a) BRAIN PENETRATION CLASSIFICATION (BPC)PS, fu,br , Vu,br , Kp,uu,cell, t1/2, BPC (Kalvass-Maurer-Pollack)
BRAIN EXPOSURE TO DRUGS<http://www.in-ADME.com/pCEL_X.html>
in-ADME Research Copyright © 2012
Nine drugs were selected to illustrate the two new features in pCEL-X <http://www.in-ADME.com/pCEL_X.html>. Bold numbers in the Table below are available experimental values used as input to predict Brain Penetration Classification (BPC). Italic values of intrinsic PAMPA permeability coefficients were calculated by pCEL-X. Italic pKa and log POCT values are the average of ADME Boxes (v4.9) and Marvin predictions. The brain unbound-drug fractions are represented by fu,br (brain homogenate method).
NEW FEATURES SAMPLE CALCULATIONS
Drugs with BPC I/Ib/II show poor brain exposure; classes III- & IV show good brain exposure.
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AMPRENAVIR
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AMPRENAVIR
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ATENOLOL
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ATENOLOL
Lit: Peff 0.2 ± 0.1
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INDINAVIR
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INDINAVIR
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IVERMECTIN
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IVERMECTIN
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METOPROLOL
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in-ADME Research Copyright © 2012
Lit: Peff 1.2 ± 0.3
METOPROLOL
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MORPHINE-6-GLUCURONIDE
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MORPHINE-6-GLUCURONIDE
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NAPROXEN
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NAPROXEN
Lit: Peff 9.0 ± 1.0page 16
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OXYCODONE
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OXYCODONE
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SAQUINAVIR
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SAQUINAVIR
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REFINEMENT OF MODELUSING Caco-2 Papp vs. pH DATA
ATENOLOL pH 4.5-8.0 DATA (Neuhoff et al. 2003)
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in-ADME Research Copyright © 2012
Simulation and Refinementof BBB, Caco-2, & PAMPA
pH-Dependent Permeability DataPrediction of Brain Penetration Classification
in-ADME ResearchpCEL-X Rev 4.0
more info at <http://www.in-ADME.com/pCEL_X.html>
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