Skip to main content
SpringerLink
Log in
Book cover

Drug Interactions in Infectious Diseases pp 613–630Cite as

Drug Interaction Considerations Throughout Drug Development

  • Chapter
  • First Online:

  • 1669 Accesses

Part of the book series: Infectious Disease ((ID))

Abstract

The objectives of a drug interaction program are to determine whether there are interactions with an NME (new molecular entity) that necessitate a dose adjustment of the NME or other drugs that it might be used with, or whether an interaction requires a contraindication or special precautions. The program should begin early in drug development so the clinical implications of interactions can be assessed adequately in clinical studies. It is important that all studies are conducted using rigorous scientific procedures. The clinical significance of interactions should be assessed based on exposure-response knowledge of the affected drug. Drug labels need to include complete information about the potential for drug interactions, including instructions for dose adjustments and special monitoring or precautions.

The views presented in this chapter do not necessarily reflect those of the FDA

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Senior K. FDA panel rejects common cold treatment. Lancet Infect Dis 2002;2:264.

    Article  PubMed  Google Scholar 

  2. Hayden FG, Herrington DT, Coats TL, Kim K, Cooper EC, Villano SA, Liu S, Hudson S, Pevear DC, Collett M, McKinlay M. Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: results of double-blind, randomized, placebo-controlled trials. Clin Infect Dis 2003;33:1523–1532.

    Article  Google Scholar 

  3. Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for Industry: Drug interaction studies- study design, data analysis, and implications for dosing and labeling (September 2006). Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for Industry.

    Google Scholar 

  4. Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for Industry: Drug metabolism/drug interaction studies in the drug development process: studies in vitro (April 1997). Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for Industry.

    Google Scholar 

  5. Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for Industry: In vivo drug metabolism/drug interaction studies—study design, data analysis, and recommendations for dosing and labeling (November 1999). U.S. Department of Health and Human Services, Food and Drug Administration.

    Google Scholar 

  6. Giacomini KM, Huang SM, Tweedie DJ, et al. Membrane transporters in drug transport. Nat Rev Drug Discov 2010;9:215–236.

    Article  PubMed  CAS  Google Scholar 

  7. Rostami-Hodjegan A, Tucker GT. Simulation and prediction of in vivo drug metabolism in human populations from in vitro data. Nat Rev Drug Discov 2007;6:140–148.

    Article  PubMed  CAS  Google Scholar 

  8. Zhao P, Zhang L, Grillo JA, et al. Applications of physiologically-based pharmacokinetic (PBPK) modeling and simulation during regulatory review. Clin Pharmacol Ther 2011;89:259–267.

    Google Scholar 

  9. Bjornsson TD, Callaghan JT, Einolf HJ, et al. The conduct of in vitro and in vivo drug-drug interaction studies: A Pharmaceutical Research and Manufacturers of America (PhRMA) perspective. Drug Metab Disp 2003;31:815–832.

    Article  CAS  Google Scholar 

  10. Zhang L, Reynolds KS, Zhao P, Huang SM. Drug interaction evaluation: an integrated part of risk assessment of therapeutics. Tox Appl Pharmacol 2010;243:134–145.

    Article  CAS  Google Scholar 

  11. Huang SM, Strong JM, Zhang L, et al. New era in drug interaction evaluations: US Food and Drug Administration update on CYP enzymes, transporters, and the guidance process. J Clin Pharmacol 2008;48:662–670.

    Article  PubMed  CAS  Google Scholar 

  12. Ayrton A, Morgan P. Role of transport proteins in drug absorption, distribution and excretion. Xenobiotica 2001;31:469–497.

    Article  PubMed  CAS  Google Scholar 

  13. Huang SM, Woodcock J. Transporters in drug development: advancing on the Critical Path. Nat Rev Drug Discov 2010;9:175–176.

    Article  PubMed  CAS  Google Scholar 

  14. Huang SM, Temple R, Throckmorton DC, Lesko LJ. Drug interaction studies: study design, data analysis, and implications for dosing and labeling. Clin Pharmacol Ther 2007;81:298–304.

    Article  PubMed  CAS  Google Scholar 

  15. Fahmi OA, Kish M, Boldt S, Obach RS. Cytochrome P450 3A4 messenger RNA is a more reliable marker than CYP3A4 activity for detecting PXR-activated induction of drug-metabolizing enzymes. Drug Metab Dispos 2010;38:1605–1611.

    Article  PubMed  CAS  Google Scholar 

  16. Zhang L, Zhang Y, Strong JM, Reynolds KS, Huang SM. A regulatory viewpoint on transporter-based drug interactions. Xenobiotica 2008;38:709–724.

    Article  PubMed  CAS  Google Scholar 

  17. Saquinavir (Invirase), product information, Genentech USA, Inc., South San Francisco, CA, 2010.

    Google Scholar 

  18. Atazanavir (Reyataz) product information. Bristol Myers Squibb, Princeton, NJ, 2010.

    Google Scholar 

  19. Slain D, Pakyz A, Israel DS, Monroe S, Polk R. Variability in activity of hepatic CYP3A4 in patients infected with HIV. Pharmacotherapy 2000;20:898–907.

    Article  PubMed  CAS  Google Scholar 

  20. Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for Industry population pharmacokinetics (February 1999). U.S. Department of Health and Human Services, Food and Drug Administration.

    Google Scholar 

  21. Stein DS and Moore KHP. Phosphorylation of nucleoside analog antiretrovirals: a review for clinicians. Pharmacotherapy 2110;21:11–34.

    Google Scholar 

  22. Frye RF, Matzke GR, Adedoyin A, Porter JA, Branch RA. Validation of the five-drug “Pittsburgh cocktail” approach for assessment of selective regulation of drug-metabolizing enzymes. Clin Pharmacol Ther 1997;62:365–376.

    Article  PubMed  CAS  Google Scholar 

  23. Christensen M, Andersson K, Dalen P, Mirghani RA, Muirhead GJ, Nordmark A, Tybring G, Wahlberg A, Yasar U, Bertilsson L. The Karolinska cocktail for phenotyping of five human cytochrome P450 enzymes. Clin Pharmacol Ther 2003;73:517–528.

    Article  PubMed  CAS  Google Scholar 

  24. Chainuvati S, Nafziger AN, Leeder JS, Gaedigk A, Kearns GL, Sellers E, Zhang Y, Kashuba ADM, Rowland E, Bertino JS. Combined phenotypic assessment of cytochrome P450 1A2, 2C9, 2C19, 2D6, and 3A, N-acetyltransferase-2, and xanthine oxidase activities with the “Cooperstown 5  +  1 cocktail”. Clin Pharmacol Ther 2003;74:437–447.

    Article  PubMed  CAS  Google Scholar 

  25. Blakey GE, Lockton JA, Perrett J, Norwood P, Russell M, Aherne A, Plume J. Pharmacokinetic and pharmacodynamic assessment of a four-probe metabolic cocktail for CYPs 1A2, 3A4, 2 C9, 2D6, and 2E1. Br J Clin Pharmacol 2004;57:162–169.

    Article  PubMed  CAS  Google Scholar 

  26. Schuirman DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the bioequivalence of average bioavailability. J Pharmacokinet Biopharm 1987;15:657–680.

    Article  Google Scholar 

  27. Nelfinavir (Viracept) product information, Agouron Pharmaceuticals, La Jolla, CA, 2010.

    Google Scholar 

  28. Williams D, Feely J. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin Pharmacokinet 2002;41:343–370.

    Article  PubMed  CAS  Google Scholar 

  29. Ritonavir (Norvir), product information, Abbott Laboratories, North Chicago IL, 2010.

    Google Scholar 

  30. Indinavir (Crixivan) product information. Merck & Co, Inc, Whitehouse Station, NJ, 2010.

    Google Scholar 

  31. Lopinavir/ritonavir (Kaletra) product information. Abbott Laboratories, North Chicago, IL, 2010.

    Google Scholar 

  32. Fosamprenavir (Lexiva) product information. GlaxoSmithKline, Research Triangle Park, NC, 2010.

    Google Scholar 

  33. Tipranavir (Aptivus) product information. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, 2010.

    Google Scholar 

  34. Darunavir (Prezista) product information. Tibotec, Raritan, NJ, 2010.

    Google Scholar 

  35. Zeldin RK, Petruschke RA. Pharmacological and therapeutic properties of ritonavir-boosted protease inhibitor therapy in HIV-infected patients. J Antimicrob Chemother 2004;53:4–9.

    Article  PubMed  CAS  Google Scholar 

  36. Luo G, Cunningham M, Kim S, et al. CYP3A4 induction by drugs: correlation between pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metab Disp 2002;30:795–804.

    Article  CAS  Google Scholar 

  37. Wang H, LeCluyse EL. Role of orphan nuclear receptors in the regulation of drug-metabolizing enzymes. Clin Pharmacokinet 2003;42:1331–1357.

    Article  PubMed  CAS  Google Scholar 

  38. Handschin C, Meyer UA. Induction of drug metabolism: the role of nuclear receptors. Pharmacol Rev 2003;55:649–673.

    Article  PubMed  CAS  Google Scholar 

  39. Huang SM, Hall SD, Watkins P, et al. Drug interactions with herbal products and grapefruit juice: a conference report. Clin Pharmacol Ther 2004;75:1–12.

    Article  PubMed  Google Scholar 

  40. Harris RZ, Jang GR, Tsunoda S. Dietary effects on drug metabolism and transport. Clin Pharmacokinet 2003;42:1071–1088.

    Article  PubMed  CAS  Google Scholar 

  41. Rogers JF, Nafziger AN, Bertino JS. Pharmacogenetics affects dosing, efficacy, and toxicity of cytochrome P450-metabolized drugs. Am J Med 2002;113:746–750.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Office of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver-Spring, MD, 20993, USA

    Kellie Schoolar Reynolds

Authors
  1. Kellie Schoolar Reynolds
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kellie Schoolar Reynolds .

Editor information

Editors and Affiliations

  1. , Infectious Diseases, GlaxoSmithKline, Research Triangle Park, 27709, North Carolina, USA

    Stephen C. Piscitelli

  2. College of Pharmacy, Dept. Pharmacy Practice, University of Illinois, Chicago, Chicago, 60612-7230, Illinois, USA

    Keith A. Rodvold

  3. , Pharmaceutical Sciences, Albany College of Pharmacy, Albany, 12208, New York, USA

    Manjunath P. Pai

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Reynolds, K.S. (2011). Drug Interaction Considerations Throughout Drug Development. In: Piscitelli, S., Rodvold, K., Pai, M. (eds) Drug Interactions in Infectious Diseases. Infectious Disease. Humana Press. https://doi.org/10.1007/978-1-61779-213-7_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-213-7_18

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-212-0

  • Online ISBN: 978-1-61779-213-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation