Webinar revisiting food drug interactions

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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

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Webinar revisiting food drug interactions

  1. 1. Make the right decisions with data you can trust<br />
  2. 2. Instructionsforattendees<br />Due to the High number of attendees : <br />Before starting <br />We will mute your microphone during the webinar<br />Use your full name for Identification<br />During the webinar<br />Use the chat for questions<br />At the End <br />We will answer them either at the end or later on by email.<br />
  3. 3. Revisiting Food-Drug interactionsusingthe ADME/DDI database®<br />19/04/2011<br />3<br />Cliquez ici pour changer le texte<br />
  4. 4. Aureus at a Glance<br />Aureus is a knowledge and information management solutions provider for the Life Science industry located in Paris. <br />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.<br />Aureus employees 20 highlevelscientists (PhD and MSc) includingscientific and IT project leaders and documentation analysts<br />Aureus is funded by institutional investors like CDC Entreprise, AXA Provate Equity, OTC Asset Management and is part of the OSEO Excellence innovation team.<br />
  5. 5. AUREUS Mission<br />To help ourcustomers in the Life Science Industry to develop new innovative and safedrugs<br />by providing<br />Solutions whichenablethem to take the best advantage of the existingscientificknowledge<br />and therefore<br />Optimizeprocesses, predict new opportunities as well as new risks of their R&D projects<br />03/12/2010<br />5<br />Webinar<br />« Makethe right decisionswith data youcantrust »<br />
  6. 6. Aureus Value Proposition<br />Weoffer a unique combination of scientific, IT, and knowledge management assets and experience to :<br />Assistcompanies in the Life Science Industry to define the scope and scientifccontext of their information needs<br />Weensure the development of highlevelscientificdatabasesfocusing on experimental data in the areas of medicinalchemistry, drugbiologics, drugsafety, ADME/TOX.<br />Weassist on the integration of suchdatabases in customers IT infrastructure or other software applications for furtheranalysis, predictions or simulations<br />Wedevelop applications to mine and visualise the data <br />
  7. 7. Aureus Selected Customers & Main projects<br />« KnowTox »<br />
  8. 8. WeGenerate & Organize Data intoKnowledge<br />19/04/2011<br />8<br />Cliquez ici pour changer le texte<br />
  9. 9. AurSCOPE ADME/DDI Knowledge Base March 2011<br />
  10. 10. Food-drug, drug-dietary supplement, drug-citrus fruit interactions <br />19/04/2011<br />10<br />Cliquez ici pour changer le texte<br />Dietary supplement<br />- St John’s Wort<br />- Echinacea<br />- Ginkgo biloba<br />Food<br />- High fat meal<br />- Standard meal<br />- Other meal<br />drug<br />Fruitjuice<br />- Grapefruit juice<br />- Other fruitjuice<br />
  11. 11. Food-drug, drug-dietary supplement, drug-juice interactions extracted from Aureus ADME/DDI database<br />19/04/2011<br />11<br />Cliquez ici pour changer le texte<br />Drug<br />Food<br />Juice<br />Dietary<br />AUC ratio <0.5<br />AUC ratio >2<br />
  12. 12. 19/04/2011<br />12<br />Cliquez ici pour changer le texte<br />Food-drug, drug-dietary supplement, drug-juice interactions extracted from Aureus ADME/DDI database<br />Drug<br />Food<br />Juice<br />Dietary<br />AUC ratio <0.5<br />AUC ratio >2<br />
  13. 13. 19/04/2011<br />13<br />Cliquez ici pour changer le texte<br />Food-drug interactions<br />
  14. 14. Drug regulatory agencies recommendations<br />19/04/2011<br />14<br />Cliquez ici pour changer le texte<br />Effect of food intake:<br />- Assessment of the effect of food on the rate and extent of absorption of a drug<br />- Ensure optimal dosing recommendations in the phase II and III clinical studies<br />1- Standardized high-fat meal<br />High-fat meal : worst case scenario of interaction<br /><ul><li>800-1000 kcal
  15. 15. 150, 250 and 500 calories from protein, carbohydrate and fat respectively</li></ul>Composition : 2 eggs fried in butter, 2 strips of bacon, 2 slices of toast with butter,<br />120 mL hash brown potatoes and 240 mL whole milk<br />2- Lighter meal<br />for drug administrated with food<br />
  16. 16. 19/04/2011<br />15<br />Cliquez ici pour changer le texte<br />Drug regulatory agencies recommendations<br />Procedure for food interaction studies:<br />- Fasted 10h<br />- Meal consumed in 30 min or less<br />- Drug with 240 mL water at +30min<br />Analysis: AUC, Cmax, Tmax , t1/2el …<br />90 percent CI (CL-90) in the equivalence limits of 80-125 percent for AUC <br />and Cmax<br /> Specific recommendation on the clinical significance if outside the limits.<br />(1) Guidance for Industry: Food-effect bioavalaibility and fed bioequivallence studies (2002)<br />(2) Guideline on the Investigation of Drug Interactions (2010)<br />
  17. 17. Aureus ADME/DDI® Knowledgebase Query<br />19/04/2011<br />16<br />Cliquez ici pour changer le texte<br /> To compare AUC ratio between drugs we focus on “High-Fat meal” interaction<br />
  18. 18. Food interaction: Change in the extent of absorption (AUC) from Aureus ADME/DDI<br />19/04/2011<br />17<br />Cliquez ici pour changer le texte<br />149 drugs<br />
  19. 19. Food effect mechanism<br />Clinically relevant food-drug interactions are generally caused by food-induced<br />change in the Bioavailability of the drug<br /> Important pharmacokinetic effect<br />Delay gastric emptying<br />Stimulate blood flow<br />Change gastrointestinal pH<br />Increase splanchnic blood flow<br />Change luminal metabolism of a drug<br />Physically or chemically interact with a dosage form or a drug substance<br />19/04/2011<br />18<br />Cliquez ici pour changer le texte<br />
  20. 20. Biopharmaceutical Classification System (BCS)<br />BCS<br />Fundamental parameters controlling the rate and extent of oral absorption :<br />Solubility<br />Gastrointestinal permeability<br />19/04/2011<br />19<br />Cliquez ici pour changer le texte<br />High permeability: absorption >90%<br />High solubility: soluble in 250 mL <br />of aqueous media (pH 1-7.5)<br />from Wu and Benet, Pharm. Res. vol.22 p.11<br />
  21. 21. Biopharmaceutical Classification System (BCS)<br />Cliquez ici pour changer le texte<br />from Wu and Benet, Pharm. Res. vol.22 p.11<br />
  22. 22. Assessment: transporters inhibition as the primary mechanism of food effect<br />19/04/2011<br />21<br />Cliquez ici pour changer le texte<br />High-fat meal effect<br />- Increase solubility and<br />efflux transporter inhibition<br /> ( Fextent)<br />- Delay gastric emptying <br />( Tmax, Cmax)<br />- Delay gastric emptying <br />( Tmax, Cmax)<br />- Influx transporter inhibition<br /> ( Fextent)<br />- Delay gastric emptying <br />( Tmax, Cmax)<br />- Increase solubility<br />- Efflux and influx <br />transporter inhibition<br />- Delay gastric emptying<br />
  23. 23. 19/04/2011<br />22<br />Cliquez ici pour changer le texte<br />Food-dietarysupplement interactions<br />
  24. 24. Drug-dietary supplement interactions<br />19/04/2011<br />23<br />Cliquez ici pour changer le texte<br />Dietary supplements:<br />What is a dietary supplement ?<br />Vitamin<br />Mineral<br />Herb or botanical<br />Amino acid<br />Enzymes or tissues from organ or gland (to supplement diet)<br />Concentrate, metabolite, constituent<br />from FDA:<br />http://www.fda.gov/food/dietarysupplements/consumerinformation/ucm110417.htm<br />
  25. 25. Drug-dietary supplement interactions<br />19/04/2011<br />24<br />Cliquez ici pour changer le texte<br />Dietary supplements with potential pharmacokinetic interactions<br />1- St John’s wort<br /> use for depression<br />Chronic administration induces CYP3A and P-gp<br /> Consequently can alter the PK of CYP3A and P-gp substrates.<br />2- Ginkgo biloba<br /> use for memory improvement<br />Inducer of CYP2C19<br />Inhibitor of P-gp and or CYP3A4 ??<br />
  26. 26. ADME/DDI®Knowledgebase Query<br />19/04/2011<br />25<br />Cliquez ici pour changer le texte<br />
  27. 27. Drug - St John’s wortinteractions from Aureus ADME/DDI<br />19/04/2011<br />26<br />Cliquez ici pour changer le texte<br />30 drugs<br />
  28. 28. Drug - Ginkgo bilobainteractions from Aureus ADME/DDI<br />19/04/2011<br />27<br />Cliquez ici pour changer le texte<br />10 drugs<br />
  29. 29. 19/04/2011<br />28<br />Cliquez ici pour changer le texte<br />Grapefruit juice interactions<br />
  30. 30. 19/04/2011<br />29<br />Cliquez ici pour changer le texte<br />Aureus ADME/DDI® Knowledgebase Query<br />
  31. 31. Drug – grapefruit juice interactions from Aureus ADME/DDI<br />19/04/2011<br />30<br />Cliquez ici pour changer le texte<br />61 drugs<br />
  32. 32. Grapefruit juice interaction mechanism<br />Significant clinically interactions  Important pharmacokinetic effect<br />CYP3A4 inhibition in the small intestine<br />Pgp inhibition<br />OATP inhibition (> Pgp inhibition)<br />19/04/2011<br />31<br />Cliquez ici pour changer le texte<br />
  33. 33. Active components in grapefruit juice<br />19/04/2011<br />32<br />Cliquez ici pour changer le texte<br />Flavonoids<br />Naringin<br />% Inhibition OATP2B1 = 39% (at 10µM) (1)<br />% Inhibition CYP3A4 = 6% (at 100µM) (2)<br />% Inhibition OATP2B1 = 28% (at 10µM) (1)<br />IC50 CYP3A4 = 87 µM (3)<br />Naringenin<br />(1) Satoh et al. Drug Metab Dispos (2005)  33:518<br />(2) Ho et al. J Pharm Pharm Sci (2001) 4:217<br />(3) Haehner et al. Arzneimittelforschung (2004)  54:78<br />
  34. 34. Active components in grapefruit juice<br />19/04/2011<br />33<br />Cliquez ici pour changer le texte<br />Furanocoumarin<br />Bergamottin<br />Ki 3A4 (HIM) = 13.3 µM (4)<br />KI (HIM) = 23.5 µM<br />Kinact (HIM) = 0.36 min-1 (4)<br />6’,7’-Dihydroxybergamottin<br />Ki 3A4 (HIM) = 3.5 µM (4)<br />KI (HIM) = 3.5 µM<br />Kinact (HIM) = 0.31 min-1 (4)<br />(4) Paine et al. Drug Metab Dispos (2004)  32:1146<br />
  35. 35. Mechanism of grapefruit juice interactions<br />19/04/2011<br />34<br />Cliquez ici pour changer le texte<br />BLOOD<br />_<br />CYP3A4<br />intestinal epithelium<br />GFJ<br />_<br />OATP<br />Pgp<br />_<br />GFJ<br />drug<br />LUMEN<br />
  36. 36. Mechanism of grapefruit juice interactions<br />19/04/2011<br />35<br />Cliquez ici pour changer le texte<br />CYP3A4 substrates<br />
  37. 37. Mechanism of grapefruit juice interactions<br />19/04/2011<br />36<br />Cliquez ici pour changer le texte<br />OATP and Pgp substrates<br />celiprolol<br />talinolol<br />fexofenadine<br />
  38. 38. AfterthisWebinar<br />An individual account will be created for each of you on www.aureus-sciences.com<br />It is unique in offering access to editorial content, Aureus data & applications and community networks. <br />Your new account will allow you to access our data and our tools including Food-Drug Interaction through AurQUESTfor free during 2 days.<br />19/04/2011<br />37<br />Food-Drug Interactions Webinar<br />
  39. 39. Special Offer for this Webinar<br />After the 2 free-trial days, we offer a special Access through the web during 1 year to data related to:<br />Metabolism<br />PK (Pharmacokinetics)<br />Drug-Drug interactions<br />Food Drug interactions<br />Our Offer: 5 000 €, one user, 12 months.<br />19/04/2011<br />38<br />Food-Drug Interactions Webinar<br />
  40. 40. Thank you for your attention<br />Aureus Sciences<br />174, Quai de Jemmapes <br />75010 Paris, FRANCE<br />www.aureus-sciences.com<br />

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