1. BRAIN EXPOSURE TO DRUGS
<http://www.in-ADME.com/pCEL_X.html>
in-ADME Research
pCEL-X Rev 4.0
(a) BRAIN PENETRATION CLASSIFICATION (BPC)
PS, fu,br , Vu,br , Kp,uu,cell, t1/2, BPC (Kalvass-Maurer-Pollack)
(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)
Presentation Copyrighted (C) 2012. in-ADME Research. All rights reserved.
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2. NEW FEATURES SAMPLE CALCULATIONS
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).
Drugs with BPC I/Ib/II show poor brain exposure; classes III- & IV show
good brain exposure.
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3. AMPRENAVIR
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4. AMPRENAVIR
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5. ATENOLOL
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6. ATENOLOL
Lit: Peff 0.2 ± 0.1
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7. INDINAVIR
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8. INDINAVIR
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9. IVERMECTIN
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10. IVERMECTIN
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11. METOPROLOL
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12. METOPROLOL
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Lit: Peff 1.2 ± 0.3 in-ADME Research Copyright © 2012

13. MORPHINE-
6-GLUCURONIDE
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14. MORPHINE-6-GLUCURONIDE
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15. NAPROXEN
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16. NAPROXEN
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Lit: Peff 9.0 ± 1.0 in-ADME Research Copyright © 2012

17. OXYCODONE
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18. OXYCODONE
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19. SAQUINAVIR
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20. SAQUINAVIR
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21. REFINEMENT OF MODEL
USING Caco-2 Papp vs. pH DATA
ATENOLOL pH 4.5-8.0 DATA (Neuhoff et al. 2003)
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25. in-ADME Research
pCEL-X Rev 4.0
more info at <http://www.in-ADME.com/pCEL_X.html>
Simulation and Refinement
of BBB, Caco-2, & PAMPA
pH-Dependent Permeability Data
Prediction of Brain Penetration Classification
in-ADME Research Copyright © 2012