In this webinar, our PharmaPendium expert, Phillip Maclaughlin introduced the new module in PharmaPendium, showing the audience how they may better understand drug-drug interactions using this newly created data source.

1. PharmaPendium: Metabolizing
Enzymes and Transporters Module
Your presenter: Philip Maclaughlin
Welcome to our webinar!
Your host: Chris Flemming

2. About Us
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3. Agenda
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• Short Introduction to PharmaPendium
• Metabolizing Enzymes & Transporters Module
• Live Demo MET Module
• Questions and requests

4. What is PharmaPendium?
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First product to offer both searchable FDA approval packages
and EMA EPARs
• 1.7M newly-searchable pages covering all of FDA history, over 70 years
(from 1938),
• Searchable EMA EPAR content (from 1995)
Used primarily for Preclinical assessment (Safety, PK, Efficacy) and Regulatory
Affairs
AERS (post-marketing events)

5. What is PharmaPendium?
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First product to bring together preclinical, clinical & post marketing data
•Normalized terminology on searches, extracted data
•Which experimental data translates, why or why not?
Over 1,200,000 extracted drug safety observations
•Normalized AE/Tox terminology mapped to Class, Target, Structural Chemistry
Over 1,300,000 extracted PK parameter data, preclinical and clinical. Normalized and
related the same way (structure, class, target)

6. Metabolizing Enzymes &Transporters (MET) Module for
PharmaPendium
Adverse drug interactions resulting from effects of drug
metabolizing enzymes and transporters.
• These drug-metabolizing enzymes (CYPs and Phase 2) and transporters, are key
players in drug/drug interactions
• Unintended/unanticipated toxicities and efficacy failures.
With our unique content assets (FDA, EMA, FDAAC), we have built a
database with unsurpassed depth.
• Containing CYPs, Phase2 enzymes, dynamic parameters (Cint, Vmax) and
transporters –
• Measured with drug as substrate, inducer or inhibitor.
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7. Metabolizing Enzymes &Transporters (MET) Module for
PharmaPendium
Extracted Content from FDA, EMA, FDAAC, journals:
All with drug as: substrate, inducer or inhibitor
Metabolites CYPs
Transporters In Vitro DDI Studies
Created, when
available
Either involved in the
metabolism or up/down
regulated by the drug,
quantitative and
qualitative data
Phase 2 Enzymes
And drug effects on
transporters
Dynamic parameters
such as CLint (Intrinsic
Clearance) and Km
(Michaelis Constant),
Vmax (Maximum rate of
reaction)
Ratio of AUC,
Clearance, etc. in
presence of another
drug.
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8. End User Problems Addressed:
What could be the result an
increase in these enzymes on
other drugs?
Which CYPs’
production is likely
stimulated when my
drug is administered?
How can I improve my
DDI models to reflect
various subject types,
doses, etc?
Which CYPs’
production is likely
inhibited when my
drug is administered?
What could be the result of a
decrease in these enzymes on
other drugs, or the health of the
patient?
Which CYPs’ are
likely to act on
my drug and
metabolize it?
At what rate? What food may
increase/decrease this CYP?
What effect can these enzymes
and transporters have on the
bioavailability of my drug within
the proposed therapeutic window?
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Metabolizing Enzymes &Transporters (MET) Module for
PharmaPendium

9. Metabolizing Enzymes &Transporters (MET) Module for
PharmaPendium
Value:
Unmatched level of
curation from a unique
data source:
More data per drug
More experimental detail
Highest quality data
Understanding potential
drug-drug interactions is
critical to today’s drug
approval process.
Drugs get hung up in the approval
process (patent time)
Drugs fail late due to unexpected
DDI’s
Drugs are withdrawn due to DDI’s
(catastrophic)
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10. Preclinical/Clinical representation of data
Example: Anticonvulsants
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11. Filters applied; CYP2C8 & as “an inhibitor”
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12. Drill down: Entire study and associated observations
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13. Selected Transporter data display
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14. Example with Aprepitant

15. Filter Using “Sources”

16. Filter Using “Study Type”
Select specific
parameters
under enzyme
inhibitor

17. Select Parameters of Interest

18. Result with Filters

19. Source Document

20. Termination of Phase IIb study due to DDI
Here is an example of
how a Phase IIb study
was terminated due to a
drug-drug interaction
A dose modification
could have prevented the
termination of the Phase
IIb study

21. Metabolizing Enzymes &Transporters (MET) Module for
PharmaPendium
Value:
Unmatched level of curation from a unique data
source:
More data per drug
More experimental detail
Highest quality data
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22. Open Discussion and Questions
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