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Webinar revisiting food drug interactions

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Context …

Context

In addition to drug-drug interactions, "Food-drug interactions" can also cause adverse drug reactions or losses of efficacy and are thus important issues to consider in the evaluation of new drug candidates.

This is why drug agencies recommend conducting food-drug studies early in the development of new drugs. For example, the FDA advises the administration of a high-fat meal with new drugs to investigate potential food effect.

Aureus' Solutions

Aureus Sciences has developed a highly structured Knowledgebase, AurSCOPE ADME/DDI®, containing pharmacokinetics, metabolism and drug interactions data including reliable information about "Food-Drug interaction" studies extracted from journal articles and FDA reviews.

Knowledge from published data can help the pharmaceutical industry improve recommendations for regulatory agencies on how drugs should be taken when eating food, and to challenge prediction of food-drug interactions.

What you will learn

Similarities and differences of regulatory agencies recommendations on food-drug interaction

New insights about food-drug interactions including herbal, fruit, and dietary interactions based on clinical outcomes

Therapeutic classes, physico-chemical properties of drugs linked with high food-drug interactions

Published in: Health & Medicine
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Transcript

  • 1. Make the right decisions with data you can trust
  • 2. Instructionsforattendees
    Due to the High number of attendees :
    Before starting
    We will mute your microphone during the webinar
    Use your full name for Identification
    During the webinar
    Use the chat for questions
    At the End
    We will answer them either at the end or later on by email.
  • 3. Revisiting Food-Drug interactionsusingthe ADME/DDI database®
    19/04/2011
    3
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  • 4. Aureus at a Glance
    Aureus is a knowledge and information management solutions provider for the Life Science industry located in Paris.
    Over the past 10 years the company has developed a unique knowledge production platform which stores, indexes and organizes critical chemical and bioactivity information including experimental vitro and vivo protocols from the public or private literature.
    Aureus employees 20 highlevelscientists (PhD and MSc) includingscientific and IT project leaders and documentation analysts
    Aureus is funded by institutional investors like CDC Entreprise, AXA Provate Equity, OTC Asset Management and is part of the OSEO Excellence innovation team.
  • 5. AUREUS Mission
    To help ourcustomers in the Life Science Industry to develop new innovative and safedrugs
    by providing
    Solutions whichenablethem to take the best advantage of the existingscientificknowledge
    and therefore
    Optimizeprocesses, predict new opportunities as well as new risks of their R&D projects
    03/12/2010
    5
    Webinar
    « Makethe right decisionswith data youcantrust »
  • 6. Aureus Value Proposition
    Weoffer a unique combination of scientific, IT, and knowledge management assets and experience to :
    Assistcompanies in the Life Science Industry to define the scope and scientifccontext of their information needs
    Weensure the development of highlevelscientificdatabasesfocusing on experimental data in the areas of medicinalchemistry, drugbiologics, drugsafety, ADME/TOX.
    Weassist on the integration of suchdatabases in customers IT infrastructure or other software applications for furtheranalysis, predictions or simulations
    Wedevelop applications to mine and visualise the data
  • 7. Aureus Selected Customers & Main projects
    « KnowTox »
  • 8. WeGenerate & Organize Data intoKnowledge
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  • 9. AurSCOPE ADME/DDI Knowledge Base March 2011
  • 10. Food-drug, drug-dietary supplement, drug-citrus fruit interactions
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    Dietary supplement
    - St John’s Wort
    - Echinacea
    - Ginkgo biloba
    Food
    - High fat meal
    - Standard meal
    - Other meal
    drug
    Fruitjuice
    - Grapefruit juice
    - Other fruitjuice
  • 11. Food-drug, drug-dietary supplement, drug-juice interactions extracted from Aureus ADME/DDI database
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    Drug
    Food
    Juice
    Dietary
    AUC ratio <0.5
    AUC ratio >2
  • 12. 19/04/2011
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    Food-drug, drug-dietary supplement, drug-juice interactions extracted from Aureus ADME/DDI database
    Drug
    Food
    Juice
    Dietary
    AUC ratio <0.5
    AUC ratio >2
  • 13. 19/04/2011
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    Food-drug interactions
  • 14. Drug regulatory agencies recommendations
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    Effect of food intake:
    - Assessment of the effect of food on the rate and extent of absorption of a drug
    - Ensure optimal dosing recommendations in the phase II and III clinical studies
    1- Standardized high-fat meal
    High-fat meal : worst case scenario of interaction
    • 800-1000 kcal
    • 15. 150, 250 and 500 calories from protein, carbohydrate and fat respectively
    Composition : 2 eggs fried in butter, 2 strips of bacon, 2 slices of toast with butter,
    120 mL hash brown potatoes and 240 mL whole milk
    2- Lighter meal
    for drug administrated with food
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    Drug regulatory agencies recommendations
    Procedure for food interaction studies:
    - Fasted 10h
    - Meal consumed in 30 min or less
    - Drug with 240 mL water at +30min
    Analysis: AUC, Cmax, Tmax , t1/2el …
    90 percent CI (CL-90) in the equivalence limits of 80-125 percent for AUC
    and Cmax
     Specific recommendation on the clinical significance if outside the limits.
    (1) Guidance for Industry: Food-effect bioavalaibility and fed bioequivallence studies (2002)
    (2) Guideline on the Investigation of Drug Interactions (2010)
  • 17. Aureus ADME/DDI® Knowledgebase Query
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     To compare AUC ratio between drugs we focus on “High-Fat meal” interaction
  • 18. Food interaction: Change in the extent of absorption (AUC) from Aureus ADME/DDI
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    149 drugs
  • 19. Food effect mechanism
    Clinically relevant food-drug interactions are generally caused by food-induced
    change in the Bioavailability of the drug
     Important pharmacokinetic effect
    Delay gastric emptying
    Stimulate blood flow
    Change gastrointestinal pH
    Increase splanchnic blood flow
    Change luminal metabolism of a drug
    Physically or chemically interact with a dosage form or a drug substance
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  • 20. Biopharmaceutical Classification System (BCS)
    BCS
    Fundamental parameters controlling the rate and extent of oral absorption :
    Solubility
    Gastrointestinal permeability
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    High permeability: absorption >90%
    High solubility: soluble in 250 mL
    of aqueous media (pH 1-7.5)
    from Wu and Benet, Pharm. Res. vol.22 p.11
  • 21. Biopharmaceutical Classification System (BCS)
    Cliquez ici pour changer le texte
    from Wu and Benet, Pharm. Res. vol.22 p.11
  • 22. Assessment: transporters inhibition as the primary mechanism of food effect
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    High-fat meal effect
    - Increase solubility and
    efflux transporter inhibition
    ( Fextent)
    - Delay gastric emptying
    ( Tmax, Cmax)
    - Delay gastric emptying
    ( Tmax, Cmax)
    - Influx transporter inhibition
    ( Fextent)
    - Delay gastric emptying
    ( Tmax, Cmax)
    - Increase solubility
    - Efflux and influx
    transporter inhibition
    - Delay gastric emptying
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    Food-dietarysupplement interactions
  • 24. Drug-dietary supplement interactions
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    Dietary supplements:
    What is a dietary supplement ?
    Vitamin
    Mineral
    Herb or botanical
    Amino acid
    Enzymes or tissues from organ or gland (to supplement diet)
    Concentrate, metabolite, constituent
    from FDA:
    http://www.fda.gov/food/dietarysupplements/consumerinformation/ucm110417.htm
  • 25. Drug-dietary supplement interactions
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    Dietary supplements with potential pharmacokinetic interactions
    1- St John’s wort
     use for depression
    Chronic administration induces CYP3A and P-gp
     Consequently can alter the PK of CYP3A and P-gp substrates.
    2- Ginkgo biloba
     use for memory improvement
    Inducer of CYP2C19
    Inhibitor of P-gp and or CYP3A4 ??
  • 26. ADME/DDI®Knowledgebase Query
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  • 27. Drug - St John’s wortinteractions from Aureus ADME/DDI
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    30 drugs
  • 28. Drug - Ginkgo bilobainteractions from Aureus ADME/DDI
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    10 drugs
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    Grapefruit juice interactions
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    Aureus ADME/DDI® Knowledgebase Query
  • 31. Drug – grapefruit juice interactions from Aureus ADME/DDI
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    61 drugs
  • 32. Grapefruit juice interaction mechanism
    Significant clinically interactions  Important pharmacokinetic effect
    CYP3A4 inhibition in the small intestine
    Pgp inhibition
    OATP inhibition (> Pgp inhibition)
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  • 33. Active components in grapefruit juice
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    Flavonoids
    Naringin
    % Inhibition OATP2B1 = 39% (at 10µM) (1)
    % Inhibition CYP3A4 = 6% (at 100µM) (2)
    % Inhibition OATP2B1 = 28% (at 10µM) (1)
    IC50 CYP3A4 = 87 µM (3)
    Naringenin
    (1) Satoh et al. Drug Metab Dispos (2005)  33:518
    (2) Ho et al. J Pharm Pharm Sci (2001) 4:217
    (3) Haehner et al. Arzneimittelforschung (2004)  54:78
  • 34. Active components in grapefruit juice
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    Furanocoumarin
    Bergamottin
    Ki 3A4 (HIM) = 13.3 µM (4)
    KI (HIM) = 23.5 µM
    Kinact (HIM) = 0.36 min-1 (4)
    6’,7’-Dihydroxybergamottin
    Ki 3A4 (HIM) = 3.5 µM (4)
    KI (HIM) = 3.5 µM
    Kinact (HIM) = 0.31 min-1 (4)
    (4) Paine et al. Drug Metab Dispos (2004)  32:1146
  • 35. Mechanism of grapefruit juice interactions
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    BLOOD
    _
    CYP3A4
    intestinal epithelium
    GFJ
    _
    OATP
    Pgp
    _
    GFJ
    drug
    LUMEN
  • 36. Mechanism of grapefruit juice interactions
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    CYP3A4 substrates
  • 37. Mechanism of grapefruit juice interactions
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    OATP and Pgp substrates
    celiprolol
    talinolol
    fexofenadine
  • 38. AfterthisWebinar
    An individual account will be created for each of you on www.aureus-sciences.com
    It is unique in offering access to editorial content, Aureus data & applications and community networks.
    Your new account will allow you to access our data and our tools including Food-Drug Interaction through AurQUESTfor free during 2 days.
    19/04/2011
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    Food-Drug Interactions Webinar
  • 39. Special Offer for this Webinar
    After the 2 free-trial days, we offer a special Access through the web during 1 year to data related to:
    Metabolism
    PK (Pharmacokinetics)
    Drug-Drug interactions
    Food Drug interactions
    Our Offer: 5 000 €, one user, 12 months.
    19/04/2011
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    Food-Drug Interactions Webinar
  • 40. Thank you for your attention
    Aureus Sciences
    174, Quai de Jemmapes
    75010 Paris, FRANCE
    www.aureus-sciences.com

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