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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.
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PharmaPendium: Metabolizing Enzymes and Transporters Module
Your presenter: Philip Maclaughlin
Welcome to our webinar!
Your host: Chris Flemming
About Us
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Agenda
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• Short Introduction to PharmaPendium
• Metabolizing Enzymes & Transporters Module
• Live Demo MET Module
• Questions and requests
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)
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)
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 adatabase 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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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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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
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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Preclinical/Clinical representation of dataExample: Anticonvulsants
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Filters applied; CYP2C8 & as “an inhibitor”
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Drill down: Entire study and associated observations
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Selected Transporter data display
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Example with Aprepitant
Filter Using “Sources”
Filter Using “Study Type”
Select specific parameters
under enzyme inhibitor
Select Parameters of Interest
Result with Filters
Source Document
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
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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Open Discussion and Questions
22Pharmapendium® and the Pharmapendium® trademark are owned and protected by Reed Elsevier Properties SA. All rights reserved
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