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Improvement in the handling of drug–drug interactions

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Abstract

Approximately one in 200 hospitalised patients has a serious adverse drug effect caused by drug–drug interactions (DDIs). Such adverse effects should be avoidable, but current information provided on DDIs is often incomplete and difficult or even impossible to translate into true risk and appropriate tangible action. Clinicians need to know the mean and maximal expected effect of a DDI on clinical endpoints, any dose adjustments required, and how to monitor tolerability and efficacy in patients subject to a DDI. To this end, improved study designs should take the objective of improving treatment explicitly into account, and any existing DDI data should be publicly accessible. Modelling needs to be used more extensively in order to quantitatively predict the effects of DDIs on clinical endpoints in patients and to relate clinical endpoint effects considered as acceptable to respective changes in experimental and clinical studies. Computer-based expert systems will be required to convert such DDI data into recommendations applicable to the individual patient. Therefore, the incorporation of DDIs in a more general procedure for personalisation of drug therapy is desirable.

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References

  1. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP (1997) Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA 277(4):301–306, Jan 22–29

    Article  PubMed  CAS  Google Scholar 

  2. Levy M, Kewitz H, Altwein W, Hillebrand J, Eliakim M (1980) Hospital admissions due to adverse drug reactions: a comparative study from Jerusalem and Berlin. Eur J Clin Pharmacol 17(1):25–31

    Article  PubMed  CAS  Google Scholar 

  3. Lazarou J, Pomeranz BH, Corey PN (1998) Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 279(15):1200–1205

    Article  PubMed  CAS  Google Scholar 

  4. Schneeweiss S, Hasford J, Gottler M, Hoffmann A, Riethling AK, Avorn J (2002) Admissions caused by adverse drug events to internal medicine and emergency departments in hospitals: a longitudinal population-based study. Eur J Clin Pharmacol 58(4):285–291

    Article  PubMed  Google Scholar 

  5. van der Hooft CS, Sturkenboom MC, van Grootheest K, Kingma HJ, Stricker BH (2006) Adverse drug reaction-related hospitalisations: a nationwide study in The Netherlands. Drug Saf 29(2):161–168

    Article  PubMed  Google Scholar 

  6. Vazquez E, Whitfield L (1997) Seldane warnings. Posit Aware 8(6):12

    Google Scholar 

  7. Backman JT, Wang JS, Wen X, Kivisto KT, Neuvonen PJ (1999) Mibefradil but not isradipine substantially elevates the plasma concentrations of the CYP3A4 substrate triazolam. Clin Pharmacol Ther 66(4):401–407

    Article  PubMed  CAS  Google Scholar 

  8. Wysowski DK, Corken A, Gallo-Torres H, Talarico L, Rodriguez EM (2001) Postmarketing reports of QT prolongation and ventricular arrhythmia in association with cisapride and Food and Drug Administration regulatory actions. Am J Gastroenterol 96(6):1698–1703

    Article  PubMed  CAS  Google Scholar 

  9. Backman JT, Kyrklund C, Neuvonen M, Neuvonen PJ (2002) Gemfibrozil greatly increases plasma concentrations of cerivastatin. Clin Pharmacol Ther 72(6):685–691

    Article  PubMed  CAS  Google Scholar 

  10. Hildebrandt A, Remmer H, Estabrook RW (1968) Cytochrome P-450 of liver microsomes-one pigment or many. Biochem Biophys Res Commun 30(6):607–612

    Article  PubMed  CAS  Google Scholar 

  11. Sjoqvist F (1965) Psychotropic drugs (2). Interaction between monoamine oxidase (MAO) inhibitors and other substances. Proc R Soc Med 58(11 Part 2):967–978

    PubMed  CAS  Google Scholar 

  12. Riegelman S, Rowland M, Epstein WL (1970) Griseofulvin-phenobarbital interaction in man. Jama 213(3):426–431

    Article  PubMed  CAS  Google Scholar 

  13. Blank H (1967) The actions and interactions of drugs: the therapeutic significance of enzyme induction. Trans St Johns Hosp Dermatol Soc 53(1):1–23

    PubMed  CAS  Google Scholar 

  14. Mathies H (1965) [Experimental studies in humans on the synergistic action of prednisolone and phenylbutazone]. Arzneimittelforschung 15(7):738–741

    PubMed  CAS  Google Scholar 

  15. Omura T, Sato R (1962) A new cytochrome in liver microsomes. J Biol Chem 237:1375–1376

    PubMed  CAS  Google Scholar 

  16. Watson JD, Crick FH (1953) Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature 171(4356):737–738

    Article  PubMed  CAS  Google Scholar 

  17. Dost FH (1953) Der Blutspiegel. Theime, Leipzig

  18. Fuhr U, Weiss M, Kroemer HK, Neugebauer G, Rameis H, Weber W et al. (1996) Systematic screening for pharmacokinetic interactions during drug development. Int J Clin Pharmacol Ther 34(4):139–151

    PubMed  CAS  Google Scholar 

  19. Baranczewski P, Stanczak A, Sundberg K, Svensson R, Wallin A, Jansson J et al. (2006) Introduction to in vitro estimation of metabolic stability and drug interactions of new chemical entities in drug discovery and development. Pharmacol Rep 58(4):453–472

    PubMed  CAS  Google Scholar 

  20. Dykens JA, Marroquin LD, Will Y (2007) Strategies to reduce late-stage drug attrition due to mitochondrial toxicity. Expert Rev Mol Diagn 7(2):161–175

    Article  PubMed  CAS  Google Scholar 

  21. Sewing A, Cawkill D (2006) High-throughput lead finding and optimisation for GPCR targets. Ernst Schering Found Symp Proc 2:249–267

    Article  PubMed  CAS  Google Scholar 

  22. Fuhr U (2007) What is the true risk of a pharmacokinetic drug-drug interaction? Eur J Clin Pharmacol 63(10):897–899

    Article  PubMed  Google Scholar 

  23. Klotz U, Beil W, Gleiter C, Drewelow B, Garbe E, Gillessen A et al. (2003) Drug interactions. Mechanisms and clinical relevance. Internist (Berl) 44(11):1444–1449

    Article  CAS  Google Scholar 

  24. Fuhr U, Jetter A, Kirchheiner J (2007) Appropriate phenotyping procedures for drug metabolizing enzymes and transporters in humans and their simultaneous use in the “cocktail” approach. Clin Pharmacol Ther 81(2):270–283

    Article  PubMed  CAS  Google Scholar 

  25. Flaherty JH, Perry HM 3rd, Lynchard GS, Morley JE (2000) Polypharmacy and hospitalization among older home care patients. J Gerontol A Biol Sci Med Sci 55(10):M554–M559

    PubMed  CAS  Google Scholar 

  26. Fulton MM, Allen ER (2005) Polypharmacy in the elderly: a literature review. J Am Acad Nurse Pract 17(4):123–132

    Article  PubMed  Google Scholar 

  27. Brown HS, Galetin A, Hallifax D, Houston JB (2006) Prediction of in vivo drug-drug interactions from in vitro data: factors affecting prototypic drug-drug interactions involving CYP2C9, CYP2D6 and CYP3A4. Clin Pharmacokinet 45(10):1035–1050

    Article  PubMed  CAS  Google Scholar 

  28. Howgate EM, Rowland Yeo K, Proctor NJ, Tucker GT, Rostami-Hodjegan A (2006) Prediction of in vivo drug clearance from in vitro data. I: impact of inter-individual variability. Xenobiotica 36(6):473–497

    Article  PubMed  CAS  Google Scholar 

  29. Collins C, Levy R, Ragueneau-Majlessi I, Hachad H (2006) Prediction of maximum exposure in poor metabolizers following inhibition of nonpolymorphic pathways. Curr Drug Metab 7(3):295–299

    Article  PubMed  CAS  Google Scholar 

  30. Steinijans VW, Hartmann M, Huber R, Radtke HW (1992) Lack of pharmacokinetic interaction as an equivalence problem. Int J Clin Pharmacol Ther Toxicol 30[Suppl 1]:S63–S68

    PubMed  Google Scholar 

  31. Grizzle AJ, Mahmood MH, Ko Y, Murphy JE, Armstrong EP, Skrepnek GH et al. (2007) Reasons provided by prescribers when overriding drug-drug interaction alerts. Am J Manag Care 13(10):573–578

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Clinical Pharmacology Unit, University of Cologne, Gleueler Str. 24, 50931, Köln, Germany

    Uwe Fuhr

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  1. Uwe Fuhr
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Correspondence to Uwe Fuhr.

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Fuhr, U. Improvement in the handling of drug–drug interactions. Eur J Clin Pharmacol 64, 167–171 (2008). https://doi.org/10.1007/s00228-007-0436-8

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  • DOI: https://doi.org/10.1007/s00228-007-0436-8

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