Skip to main content
SpringerLink
Log in

Drug interactions result from a number of underlying pharmacokinetic and pharmacodynamic mechanisms

  • Drug Reactions and Interactions
  • Published:
Drugs & Therapy Perspectives Aims and scope Submit manuscript

Abstract

In order to predict and prevent drug interactions in clinical practice, it is essential that healthcare professionals have a good knowledge of the main mechanisms underlying drug–drug and drug–food interactions. Although many theoretical interactions are not clinically significant, the potential for clinically relevant drug interactions is increasing as the population ages, the use of polypharmacy becomes even more common and new drugs are developed.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Brewer L, Williams D. Clinically relevant drug-drug and drug-food interactions: underlying mechanisms and regulatory requirements for drug licensing. Phar Med. 2013;27(1):9–23.

    Article  Google Scholar 

  2. Zhang L, Reynolds KS, Zhao P, et al. Drug interactions evaluation: an integrated part of risk assessment of therapeutics. Toxicol Appl Pharmacol. 2010;243(2):134–45.

    Article  PubMed  CAS  Google Scholar 

  3. Feely J, Barry M. Adverse drug interactions. Clin Med. 2005;5(1):19–22.

    Article  PubMed  Google Scholar 

  4. Kongkaew C, Noyce PR, Ashcroft DM. Hospital admissions associated with adverse drug reactions: a systematic review of prospective observational studies. Ann Pharmacother. 2008;42(7):1017–25.

    Article  PubMed  Google Scholar 

  5. Reimche L, Forster AJ, van Walraven C. Incidence and contributors to potential drug-drug interactions in hospitalized patients. J Clin Pharmacol. 2011;51(7):1043–50.

    Article  PubMed  CAS  Google Scholar 

  6. D’Arcy PF. Drug interactions in vitro. Ir J Med Sci. 1974;143(1):93–109.

    Article  Google Scholar 

  7. Cozza KL, Armstrong SC, Oesterheld JR. Concise guide to drug interaction principles for medical practice: cytochrome P450s, UGTs, p-glycoproteins. 2nd ed. Washington, DC: American Psychiatric Association; 2003.

    Google Scholar 

  8. Eichelbaum M, Burk O. CYP3A genetics in drug metabolism. Nat Med. 2001;7(3):285–7.

    Article  PubMed  CAS  Google Scholar 

  9. Lin JH, Lu AY. Inhibition and induction of cytochrome P450 and the clinical implications. Clin Pharmacokinet. 1998;35:361–90.

    Article  PubMed  CAS  Google Scholar 

  10. Shitara Y, Horie T, Sugiyama Y. Transporters as a determinant of drug clearance and tissue distribution. Eur J Pharm Sci. 2006;27(5):425–46.

    Article  PubMed  CAS  Google Scholar 

  11. Han HK. Role of transporters in drug interactions. Arch Pharm Res. 2011;34(11):1865–77.

    Article  PubMed  CAS  Google Scholar 

  12. Zhang Y, Benet LZ. The gut as a barrier to drug absorption: combined role of cytochrome P450 3A and P-glycoprotein. Clin Pharmacokinet. 2001;40:159–68.

    Article  PubMed  CAS  Google Scholar 

  13. Kim RB, Wandel C, Leake B, et al. Interrelationship between substrates and inhibitors of human CYP3A and p-glycoprotein. Pharm Res. 1999;16:408–14.

    Article  PubMed  CAS  Google Scholar 

  14. Schepkens H, Vanholder R, Billiouw JM, et al. Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone: an analysis of 25 cases. Am J Med. 2001;110(6):438–41.

    Article  PubMed  CAS  Google Scholar 

  15. Piper JM, Ray WA, Daugherty JR, et al. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991;114:735–40.

    Article  PubMed  CAS  Google Scholar 

  16. Van der Woude HJ, Zaagsma J, Postma DS, et al. Detrimental effects of β-blockers in COPD: a concern for nonselective β-blockers. Chest. 2005;127:818–24.

    Article  PubMed  Google Scholar 

  17. Seymour RM, Routledge PA. Important drug-drug interactions in the elderly. Drugs Aging. 1998;12(6):485–94.

    Article  PubMed  CAS  Google Scholar 

  18. Won CS, Oberlies NH, Paine MF. Influence of dietary substances on intestinal drug metabolism and transport. Curr Drug Metab. 2010;11(9):778–92.

    Article  PubMed  CAS  Google Scholar 

  19. Won CS, Oberlies NH, Paine MF. Mechanisms underlying food–drug interactions: inhibition of intestinal metabolism and transport. Pharmacol Ther. 2012;136(2):186–201.

    Article  PubMed  CAS  Google Scholar 

  20. Mandlekar S, Hong JL, Kong AN. Modulation of metabolic enzymes by dietary phytochemicals: a review of mechanisms underlying beneficial versus unfavorable effects. Curr Drug Metab. 2006;7(6):661–75.

    Article  PubMed  CAS  Google Scholar 

  21. Rodriguez-Fragoso L, Martinez-Arismendi JL, Orozco-Bustos D, et al. Potential risks resulting from fruit/vegetable-drug interactions: effects on drug-metabolizing enzymes and drug transporters. J Food Sci. 2011;76(4):112–24.

    Article  Google Scholar 

  22. Satoh H, Yamashita F, Tsujimoto M, et al. Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos. 2005;33(4):518–23.

    Article  PubMed  CAS  Google Scholar 

  23. Magro L, Moretti U, Leone R. Epidemiology and characteristics of adverse drug reactions caused by drug–drug interactions. Expert Opin Drug Saf. 2012;11(1):83–94.

    Article  PubMed  CAS  Google Scholar 

  24. Shi S, Mörike K, Klotz U. The clinical implications of ageing for rational drug therapy. Eur J Clin Pharmacol. 2008;64:183–99.

    Article  PubMed  Google Scholar 

  25. Schwartz JB. The current state of knowledge on age, sex, and their interactions on clinical pharmacology. Clin Pharmacol Ther. 2007;82:87–96.

    Article  PubMed  CAS  Google Scholar 

  26. Tobias D. Age-related changes in pharmacokinetics and pharmacodynamics: a review. Consult Pharm. 2004;19:736–9.

    Article  PubMed  Google Scholar 

Download references

Disclosure

This article was adapted from Pharmaceutical Medicine 2013;27(1):9–23 [1]. The preparation of these articles was not supported by any external funding.

Author information

Authors and Affiliations

    Consortia

    Adis Medical Writers

    Rights and permissions

    Reprints and permissions

    About this article

    Cite this article

    Adis Medical Writers. Drug interactions result from a number of underlying pharmacokinetic and pharmacodynamic mechanisms. Drugs Ther Perspect 29, 217–222 (2013). https://doi.org/10.1007/s40267-013-0047-7

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s40267-013-0047-7

    Keywords

    Search

    Navigation