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PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
PharmaPendium: Metabolizing enzymes and transporters May 14 2013
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PharmaPendium: Metabolizing enzymes and transporters May 14 2013

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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 …

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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  • Aprepitant is a substance P/neurokinin 1 (NK1) receptor antagonist. In this example we would like to investigate data with relate to DDIs with Aprepitant. Under “Clinical Data”, we see a large number of results. To get to a more specific subset of results, we will use the filters to narrow this down further. We would like to search for DDI studies (from FDA approval packages only) that were done in humans where the “Study Type” was an enzyme inhibitor and the parameters pertain to changes in concentration of drugs.
  • First we will go under “Source Document” and select for FDA Approval Packages only.
  • Go under “Enzyme Inhibitor (in vivo)” and select specific parameters.
  • All of the parameters related to concentration are selected above.
  • Click on the “Source Document” of result #6 since a 2 fold difference in concentration ration was observed upon co-administration with Aprepitant and Dexamethasone.
  • In this scenario, we land on the page which has a summary of clinical findings. Scroll down to find the section where the drug-drug interaction data was extracted.
  • Here we find the paragraph from where the data was extracted. The first line of the paragraph indicates how a Phase IIb study had to be terminated due to a DDI with dexamethasone. Interestingly, at the end of the paragraph, it states that an adjustment in the dosing regimen was performed in order to reduce the occurrence of adverse events. This type of learning from past mistakes can be critical in helping a Sponsor design studies on drugs which may be similar to Aprepitant, thus potentially saving the Sponsor millions of dollars in costs and a few years.
  • Transcript

    • 1. PharmaPendium: MetabolizingEnzymes and Transporters ModuleYour presenter: Philip MaclaughlinWelcome to our webinar!Your host: Chris Flemming
    • 2. About Us2
    • 3. Agenda3• Short Introduction to PharmaPendium• Metabolizing Enzymes & Transporters Module• Live Demo MET Module• Questions and requests
    • 4. What is PharmaPendium?4First product to offer both searchable FDA approval packagesand 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 RegulatoryAffairsAERS (post-marketing events)
    • 5. What is PharmaPendium?5First 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 ChemistryOver 1,300,000 extracted PK parameter data, preclinical and clinical. Normalized andrelated the same way (structure, class, target)
    • 6. Metabolizing Enzymes &Transporters (MET) Module forPharmaPendiumAdverse drug interactions resulting from effects of drugmetabolizing enzymes and transporters.• These drug-metabolizing enzymes (CYPs and Phase 2) and transporters, are keyplayers 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) andtransporters –• Measured with drug as substrate, inducer or inhibitor.6
    • 7. Metabolizing Enzymes &Transporters (MET) Module forPharmaPendiumExtracted Content from FDA, EMA, FDAAC, journals:All with drug as: substrate, inducer or inhibitorMetabolites CYPsTransporters In Vitro DDI StudiesCreated, whenavailableEither involved in themetabolism or up/downregulated by the drug,quantitative andqualitative dataPhase 2 EnzymesAnd drug effects ontransportersDynamic parameterssuch as CLint (IntrinsicClearance) and Km(Michaelis Constant),Vmax (Maximum rate ofreaction)Ratio of AUC,Clearance, etc. inpresence of anotherdrug.7
    • 8. End User Problems Addressed:What could be the result anincrease in these enzymes onother drugs?Which CYPs’production is likelystimulated when mydrug is administered?How can I improve myDDI models to reflectvarious subject types,doses, etc?Which CYPs’production is likelyinhibited when mydrug is administered?What could be the result of adecrease in these enzymes onother drugs, or the health of thepatient?Which CYPs’ arelikely to act onmy drug andmetabolize it?At what rate? What food mayincrease/decrease this CYP?What effect can these enzymesand transporters have on thebioavailability of my drug withinthe proposed therapeutic window?8Metabolizing Enzymes &Transporters (MET) Module forPharmaPendium
    • 9. Metabolizing Enzymes &Transporters (MET) Module forPharmaPendiumValue:Unmatched level ofcuration from a uniquedata source:More data per drugMore experimental detailHighest quality dataUnderstanding potentialdrug-drug interactions iscritical to today’s drugapproval process.Drugs get hung up in the approvalprocess (patent time)Drugs fail late due to unexpectedDDI’sDrugs are withdrawn due to DDI’s(catastrophic)9
    • 10. Preclinical/Clinical representation of dataExample: Anticonvulsants10
    • 11. Filters applied; CYP2C8 & as “an inhibitor”11
    • 12. Drill down: Entire study and associated observations12
    • 13. Selected Transporter data display13
    • 14. Example with Aprepitant
    • 15. Filter Using “Sources”
    • 16. Filter Using “Study Type”Select specificparametersunder enzymeinhibitor
    • 17. Select Parameters of Interest
    • 18. Result with Filters
    • 19. Source Document
    • 20. Termination of Phase IIb study due to DDIHere is an example ofhow a Phase IIb studywas terminated due to adrug-drug interactionA dose modificationcould have prevented thetermination of the PhaseIIb study
    • 21. Metabolizing Enzymes &Transporters (MET) Module forPharmaPendiumValue:Unmatched level of curation from a unique datasource:More data per drugMore experimental detailHighest quality data21
    • 22. Open Discussion and Questions22Pharmapendium® and the Pharmapendium® trademark are owned and protected by Reed Elsevier Properties SA. All rights reserved

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