Skip to main content

Abstract

A drug interaction is a situation in which a drug, food or other extrinsic and intrinsic factors affect the activity of a medication, i.e. the effects of the medication are increased or decreased, or the combination of substances produces a new effect that neither of them produces on its own. Thereby often the efficacy or toxicity of a medication is changed.

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

Access this chapter

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
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
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

Institutional subscriptions

References

  1. Ingelman-Sundberg M (2001) Pharmacogenetics: an opportunity for a safer and more efficient pharmacotherapy. J Intern Med 250:186–200

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Marroum PJ, Uppoor RS, Parmelee T et al (2000) In vivo drug-drug interaction studies -a survey of all new molecular entities approved from 1987 to 1997. Clin Pharmacol Ther 68:280–285

    Article  CAS  PubMed  Google Scholar 

  4. EMEA (2012) Guidance on the investigation of drug interactions. (http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/07/WC500129606.pdf)

  5. FDA (2012) Drug interaction studies – study design, data analysis, and implications for dosing and labeling Recommendations. (http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm292362.pdf)

  6. Johnell K, Klarin I (2007) The relationship between number of drugs and potential drug-drug interactions in the elderly: a study of over 600,000 elderly patients from the Swedish Prescribed Drug Register. Drug Saf 30:911–918

    Article  PubMed  Google Scholar 

  7. Buajordet I, Ebbesen J, Erikssen J et al (2001) Fatal adverse drug events: the paradox of drug treatment. J Intern Med 250:327–341

    Article  CAS  PubMed  Google Scholar 

  8. Goldberg RM, Mabee J, Chan L, Wong S (1996) Drug-drug and drug-disease interactions in the ED: analysis of a high-risk population. Am J Emerg Med 14:447–450

    Article  CAS  PubMed  Google Scholar 

  9. Dresser GK, Spence JD, Bailey DG (2000) Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 38:41–57

    Article  CAS  PubMed  Google Scholar 

  10. Routledge PA, O’Mahony MS, Woodhouse KW (2004) Adverse drug reactions in elderly patients. Br J Clin Pharmacol 57:121–126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Beijnen JH, Schellens JH (2004) Drug interactions in oncology. Lancet Oncol 5:489–496

    Article  CAS  PubMed  Google Scholar 

  12. Smith RG (2009) An appraisal of potential drug interactions in cigarette smokers and alcohol drinkers. J Am Podiatr Med Assoc 99:81–88

    Article  PubMed  Google Scholar 

  13. Staffa JA, Chang J, Green L (2002) Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med 346:539–540

    Article  PubMed  Google Scholar 

  14. Gugler R, Allgayer H (1990) Effects of antacids on the clinical pharmacokinetics of drugs. An update. Clin Pharmacokinet 18:210–219

    Article  CAS  PubMed  Google Scholar 

  15. Rawashdeh NM, al-Hadidi HF, Irshaid YM, Battah AK (1993) Gastrointestinal dialysis of digoxin using cholestyramine. Pharmacol Toxicol 72:245–248

    Article  CAS  PubMed  Google Scholar 

  16. Jones NS, Quraishi S, Mason JD (1997) The nasal delivery of systemic drugs. Int J Clin Pract 51:308–311

    CAS  PubMed  Google Scholar 

  17. Vora JP, Burch A, Peters JR, Owens DR (1993) Absorption of radiolabelled soluble insulin in type 1 (insulin-dependent) diabetes: influence of subcutaneous blood flow and anthropometry. Diabet Med 10:736–743

    Article  CAS  PubMed  Google Scholar 

  18. Melander A (1978) Influence of food on the bioavailability of drugs. Clin Pharmacokinet 3:337–351

    Article  CAS  PubMed  Google Scholar 

  19. Ptachcinski RJ, Venkataramanan R, Rosenthal JT et al (1985) The effect of food on cyclosporine absorption. Transplantation 40:174–176

    Article  CAS  PubMed  Google Scholar 

  20. Liedholm H, Melander A (1986) Concomitant food intake can increase the bioavailability of propranolol by transient inhibition of its presystemic primary conjugation. Clin Pharmacol Ther 40:29–36

    Article  CAS  PubMed  Google Scholar 

  21. Welling PG, Kendall MJ, Dean S et al (1980) Effect of food on the bioavailability of alafosfalin, a new antibacterial agent. J Antimicrob Chemother 6:373–379

    Article  CAS  PubMed  Google Scholar 

  22. Fasano M, Curry S, Terreno E et al (2005) The extraordinary ligand binding properties of human serum albumin. IUBMB Life 57:787–796

    Article  CAS  PubMed  Google Scholar 

  23. Bergogne-Berezin E (2002) Clinical role of protein binding of quinolones. Clin Pharmacokinet 41:741–750

    Article  CAS  PubMed  Google Scholar 

  24. Wise R (1983) Protein binding of beta-lactams: the effects on activity and pharmacology particularly tissue penetration. II. Studies in man. J Antimicrob Chemother 12:105–118

    Article  CAS  PubMed  Google Scholar 

  25. Lindup WE, Orme MC (1981) Clinical pharmacology: plasma protein binding of drugs. Br Med J (Clin Res Ed) 282:212–214

    Article  CAS  Google Scholar 

  26. Dasgupta A (2002) Clinical utility of free drug monitoring. Clin Chem Lab Med 40:986–993

    Article  CAS  PubMed  Google Scholar 

  27. Odell GB (1959) The dissociation of bilirubin from albumin and its clinical implications. J Pediatr 55:268–279

    Article  CAS  PubMed  Google Scholar 

  28. Padowski JM, Pollack GM (2010) Pharmacokinetic and pharmacodynamic implications of P-glycoprotein modulation. Methods Mol Biol 596:359–384

    Article  CAS  PubMed  Google Scholar 

  29. Schinkel AH, Jonker JW (2003) Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev 55:3–29

    Article  CAS  PubMed  Google Scholar 

  30. Greiner B, Eichelbaum M, Fritz P et al (1999) The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J Clin Invest 104:147–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kobayashi M, Saitoh H, Yamaguchi M et al (2005) Relationship between loperamide-induced sedative effect and digoxin pharmacokinetics in healthy Japanese subjects. Pharm Res 22:413–418

    Article  CAS  PubMed  Google Scholar 

  32. Goda K, Bacso Z, Szabo G (2009) Multidrug resistance through the spectacle of P-glycoprotein. Curr Cancer Drug Targets 9:281–297

    Article  CAS  PubMed  Google Scholar 

  33. Luna-Tortos C, Fedrowitz M, Loscher W (2010) Evaluation of transport of common antiepileptic drugs by human multidrug resistance-associated proteins (MRP1,2 and 5) that are overexpressed in pharmacoresistant epilepsy. Neuropharmacology 58(7):1019–1032

    Article  CAS  PubMed  Google Scholar 

  34. Liang XJ, Aszalos A (2006) Multidrug transporters as drug targets. Curr Drug Targets 7:911–921

    Article  CAS  PubMed  Google Scholar 

  35. Fox E, Bates SE (2007) Tariquidar (XR9576): a P-glycoprotein drug efflux pump inhibitor. Expert Rev Anticancer Ther 7:447–459

    Article  CAS  PubMed  Google Scholar 

  36. Kalra BS (2007) Cytochrome P450 enzyme isoforms and their therapeutic implications: an update. Indian J Med Sci 61:102–116

    Article  PubMed  Google Scholar 

  37. McGinnity DF, Riley RJ (2001) Predicting drug pharmacokinetics in humans from in vitro metabolism studies. Biochem Soc Trans 29:135–139

    Article  CAS  PubMed  Google Scholar 

  38. Wei P, Zhang J, Egan-Hafley M et al (2000) The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism. Nature 407:920–923

    Article  CAS  PubMed  Google Scholar 

  39. Xie W, Barwick JL, Simon CM et al (2000) Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes Dev 14:3014–3023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tanaka E, Hisawa S (1999) Clinically significant pharmacokinetic drug interactions with psychoactive drugs: antidepressants and antipsychotics and the cytochrome P450 system. J Clin Pharm Ther 24:7–16

    Article  CAS  PubMed  Google Scholar 

  41. Flockhart D (2007) Drug interactions: cytochrome P450 drug interaction table. Indiana University School of Medicine. http://medicine.iupui.edu/clinpharm/ddis/

  42. Brosen K (2007) Sex differences in pharmacology. Ugeskr Laeger 169:2408–2411

    PubMed  Google Scholar 

  43. Snawder JE, Lipscomb JC (2000) Interindividual variance of cytochrome P450 forms in human hepatic microsomes: correlation of individual forms with xenobiotic metabolism and implications in risk assessment. Regul Toxicol Pharmacol 32:200–209

    Article  CAS  PubMed  Google Scholar 

  44. Li XQ, Andersson TB, Ahlstrom M, Weidolf L (2004) Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos 32:821–827

    Article  CAS  PubMed  Google Scholar 

  45. Muck W (2000) Clinical pharmacokinetics of cerivastatin. Clin Pharmacokinet 39:99–116

    Article  CAS  PubMed  Google Scholar 

  46. Altmann D, Eggmann U, Ammann P (2008) Drug induced QT prolongation. Wien Klin Wochenschr 120:128–135

    Article  CAS  PubMed  Google Scholar 

  47. Zeitlinger M, Muller M (2003) Clinico-pharmacologic explanation models of cerivastatin associated rhabdomyolysis. Wien Med Wochenschr 153:250–254

    Article  PubMed  Google Scholar 

  48. Nivoix Y, Ubeaud-Sequier G, Engel P et al (2009) Drug-drug interactions of triazole antifungal agents in multimorbid patients and implications for patient care. Curr Drug Metab 10:395–409

    Article  CAS  PubMed  Google Scholar 

  49. Hesse LM, von Moltke LL, Greenblatt DJ (2003) Clinically important drug interactions with zopiclone, Zolpidem and zaleplon. CNS Drugs 17:513–532

    Article  CAS  PubMed  Google Scholar 

  50. Staatz CE, Tett SE (2004) Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. Clin Pharmacokinet 43:623–653

    Article  CAS  PubMed  Google Scholar 

  51. Kelly P, Kahan BD (2002) Review: metabolism of immunosuppressant drugs. Curr Drug Metab 3:275–287

    Article  CAS  PubMed  Google Scholar 

  52. Ruschitzka F, Meier PJ, Turina M et al (2000) Acute heart transplant rejection due to Saint John’s wort. Lancet 355:548–549

    Article  CAS  PubMed  Google Scholar 

  53. Markowitz JS, Donovan JL, DeVane CL et al (2003) Effect of St John’s wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 290:1500–1504

    Article  CAS  PubMed  Google Scholar 

  54. Burakgazi E, Harden C, Kelly JJ (2009) Contraception for women with epilepsy. Rev Neurol Dis 6:E62–E67

    PubMed  Google Scholar 

  55. Mars H (1974) Levodopa, carbidopa, and pyridoxine in Parkinson disease. Metabolic interactions. Arch Neurol 30:444–447

    Article  CAS  PubMed  Google Scholar 

  56. Gallant JE (1998) A review of dual protease inhibitor therapy. Hopkins HIV Rep 10(1):4–5

    Google Scholar 

  57. Bonate PL, Reith K, Weir S (1998) Drug interactions at the renal level. Implications for drug development. Clin Pharmacokinet 34:375–404

    Article  CAS  PubMed  Google Scholar 

  58. Frisk AR, Diding N, Wallmark G (1952) Influence of probenecid on serum penicillin concentration after oral administration of penicillin. Scand J Clin Lab Invest 4:83–88

    Article  CAS  PubMed  Google Scholar 

  59. Frenia ML, Long KS (1992) Methotrexate and nonsteroidal antiinflammatory drug interactions. Ann Pharmacother 26:234–237

    CAS  PubMed  Google Scholar 

  60. Proudfoot AT, Krenzelok EP, Vale JA (2004) Position paper on urine alkalinization. J Toxicol Clin Toxicol 42:1–26

    Article  CAS  PubMed  Google Scholar 

  61. Hansten PD, Hayton WL (1980) Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 20:326–331

    Article  CAS  PubMed  Google Scholar 

  62. Zeiler HJ (1985) Influence of pH and human urine on the antibacterial activity of ciprofloxacin, norfloxacin and ofloxacin. Drugs Exp Clin Res 11:335–338

    CAS  PubMed  Google Scholar 

  63. Cheer K, Shearman C, Jude EB (2009) Managing complications of the diabetic foot. BMJ 339:b4905

    Article  PubMed  Google Scholar 

  64. Tam-McDevitt J (2008) Polypharmacy, aging, and cancer. Oncology (Williston Park) 22:1052–1055, discussion 1055, 1058, 1060

    Google Scholar 

  65. Ament PW, Bertolino JG, Liszewski JL (2000) Clinically significant drug interactions. Am Fam Physician 61:1745–1754

    CAS  PubMed  Google Scholar 

  66. Hyatt JM, McKinnon PS, Zimmer GS, Schentag JJ (1995) The importance of pharmacokinetic/ pharmacodynamic surrogate markers to outcome. Focus on antibacterial agents. Clin Pharmacokinet 28:143–160

    Article  CAS  PubMed  Google Scholar 

  67. Toutain PL, del Castillo JR, Bousquet-Melou A (2002) The pharmacokinetic-pharmacodynamic approach to a rational dosage regimen for antibiotics. Res Vet Sci 73:105–114

    Article  CAS  PubMed  Google Scholar 

  68. Nicolau DP (2001) Predicting antibacterial response from pharmacodynamic and pharmacokinetic profiles. Infection 29(Suppl 2):11–15

    CAS  PubMed  Google Scholar 

  69. Frimodt-Moller N (2002) How predictive is PK/PD for antibacterial agents? Int J Antimicrob Agents 19:333–339

    Article  CAS  PubMed  Google Scholar 

  70. Vogelman B, Gudmundsson S, Leggett J et al (1988) Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model. J Infect Dis 158:831–847

    Article  CAS  PubMed  Google Scholar 

  71. Bradley C (2001) Erythromycin as a gastrointestinal prokinetic agent. Intensive Crit Care Nurs 17:117–119

    Article  CAS  PubMed  Google Scholar 

  72. Laberge P, Martineau P (1997) Clarithromycin-induced digoxin intoxication. Ann Pharmacother 31:999–1002

    CAS  PubMed  Google Scholar 

  73. Morton MR, Cooper JW (1989) Erythromycin-induced digoxin toxicity. DICP 23:668–670

    CAS  PubMed  Google Scholar 

  74. Orme ML, Back DJ (1990) Factors affecting the enterohepatic circulation of oral contraceptive steroids. Am J Obstet Gynecol 163:2146–2152

    Article  CAS  PubMed  Google Scholar 

  75. Flockhart DA, Desta Z, Mahal SK (2000) Selection of drugs to treat gastro-oesophageal reflux disease: the role of drug interactions. Clin Pharmacokinet 39:295–309

    Article  CAS  PubMed  Google Scholar 

  76. Barton TD, Fishman NO, Weiner MG et al (2005) High rate of coadministration of di- or bivalent cation-containing compounds with oral fluoroquinolones: risk factors and potential implications. Infect Control Hosp Epidemiol 26:93–99

    Article  PubMed  Google Scholar 

  77. Neuvonen PJ (1976) Interactions with the absorption of tetracyclines. Drugs 11:45–54

    Article  CAS  PubMed  Google Scholar 

  78. Cohen KA, Lautenbach E, Weiner MG et al (2008) Coadministration of oral levofloxacin with agents that impair absorption: impact on antibiotic resistance. Infect Control Hosp Epidemiol 29:975–977

    Article  PubMed  Google Scholar 

  79. Van Der Meer JW, Keuning JJ, Scheijgrond HW et al (1980) The influence of gastric acidity on the bio-availability of ketoconazole. J Antimicrob Chemother 6:552–554

    Article  Google Scholar 

  80. Craig WA, Kunin CM (1976) Significance of serum protein and tissue binding of antimicrobial agents. Annu Rev Med 27:287–300

    Article  CAS  PubMed  Google Scholar 

  81. Merrikin DJ, Briant J, Rolinson GN (1983) Effect of protein binding on antibiotic activity in vivo. J Antimicrob Chemother 11:233–238

    Article  CAS  PubMed  Google Scholar 

  82. Beer J, Wagner CC, Zeitlinger M (2009) Protein binding of antimicrobials: methods for quantification and for investigation of its impact on bacterial killing. AAPS J 11:1–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Granfors MT, Backman JT, Neuvonen M, Neuvonen PJ (2004) Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism. Clin Pharmacol Ther 76:598–606

    Article  CAS  PubMed  Google Scholar 

  84. Wen X, Wang JS, Backman JT et al (2002) Trimethoprim and sulfamethoxazole are selective inhibitors of CYP2C8 and CYP2C9, respectively. Drug Metab Dispos 30:631–635

    Article  CAS  PubMed  Google Scholar 

  85. Weber A, Kaplan M, Chughtai SA et al (2001) CYP3A inductive potential of the rifamycins, rifabutin and rifampin, in the rabbit. Biopharm Drug Dispos 22:157–168

    Article  CAS  PubMed  Google Scholar 

  86. Glaeser H, Drescher S, Eichelbaum M, Fromm MF (2005) Influence of rifampicin on the expression and function of human intestinal cytochrome P450 enzymes. Br J Clin Pharmacol 59:199–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Niemi M, Backman JT, Neuvonen M, Neuvonen PJ (2003) Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide. Diabetologia 46:347–351

    Article  CAS  PubMed  Google Scholar 

  88. Bending MR, Skacel PO (1977) Rifampicin and methadone withdrawal. Lancet 1:1211

    Article  CAS  PubMed  Google Scholar 

  89. Kharasch ED, Russell M, Mautz D et al (1997) The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions. Anesthesiology 87:36–50

    Article  CAS  PubMed  Google Scholar 

  90. Gascon MP, Dayer P, Waldvogel F (1989) Drug interactions of midazolam. Schweiz Med Wochenschr 119:1834–1836

    CAS  PubMed  Google Scholar 

  91. Rieder MJ, Spino M (1988) The theophylline-erythromycin interaction. J Asthma 25:195–204

    Article  CAS  PubMed  Google Scholar 

  92. Jokinen MJ, Olkkola KT, Ahonen J, Neuvonen PJ (2003) Effect of ciprofloxacin on the pharmacokinetics of ropivacaine. Eur J Clin Pharmacol 58:653–657

    CAS  PubMed  Google Scholar 

  93. Raaska K, Neuvonen PJ (2000) Ciprofloxacin increases serum clozapine and N-desmethylclo-zapine: a study in patients with schizophrenia. Eur J Clin Pharmacol 56:585–589

    Article  CAS  PubMed  Google Scholar 

  94. Shakeri-Nejad K, Stahlmann R (2006) Drug interactions during therapy with three major groups of antimicrobial agents. Expert Opin Pharmacother 7:639–651

    Article  CAS  PubMed  Google Scholar 

  95. Iannini PB (2002) Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval. Expert Opin Drug Saf 1:121–128

    Article  CAS  PubMed  Google Scholar 

  96. Ray WA, Murray KT, Meredith S et al (2004) Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med 351:1089–1096

    Article  CAS  PubMed  Google Scholar 

  97. Cox VC, Zed PJ (2004) Once-daily cefazolin and probenecid for skin and soft tissue infections. Ann Pharmacother 38:458–463

    Article  CAS  PubMed  Google Scholar 

  98. Pea F, Furlanut M (2001) Pharmacokinetic aspects of treating infections in the intensive care unit: focus on drug interactions. Clin Pharmacokinet 40:833–868

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Markus Zeitlinger .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Zeitlinger, M. (2016). Drug Interactions. In: Müller, M. (eds) Clinical Pharmacology: Current Topics and Case Studies. Springer, Cham. https://doi.org/10.1007/978-3-319-27347-1_17

Download citation

Publish with us

Policies and ethics