Skip to main content
SpringerLink
Log in

Pharmacodynamic Drug–Drug Interactions

  • Reference work entry
Drug Discovery and Evaluation: Methods in Clinical Pharmacology

Abstract

Pharmacodynamic drug–drug interactions occur when one drug (A) alters the effects of another drug (B) without affecting its pharmacokinetics.

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

Access this chapter

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 549.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 549.99
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 AND FURTHER READING

  • Alain LWP, Zhanga WY (1998) What lessons can be learnt from withdrawal of mibefradil from the market? Lancet 351

    Google Scholar 

  • Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer N; IMPACT Investigators. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 10;350(24):2441–2451

    Google Scholar 

  • Ariens EJ, Van Rossum JM, Simonis AM (1956) A theoretical basis of molecular pharmacology. Arzneimittelforsch 6:282–293, 611–621, 737–746

    CAS  PubMed  Google Scholar 

  • Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. British Journal of Pharmacology 14:48–58

    CAS  Google Scholar 

  • Belz GG, Butzer R, Kober S, Mutschler E (2002) Pharmacodynamic studies on the AT1 antagonists irbesartan and candesartan basing on angiotensin II dose–response in humans. Journal of Cardiovascular Pharmacology 39:561–568

    Article  CAS  PubMed  Google Scholar 

  • Bentué-Ferrer D, Tribut O, Polard E, Allain H (2003) Clinically significant drug interactions with cholinesterase inhibitors: a guide for neurologists. CNS Drugs 17(13):947–963

    Article  PubMed  Google Scholar 

  • Berenbaum MC (1978) A method for testing synergy with any number of agents. The Journal of Infectious Diseases 137:122–130

    CAS  PubMed  Google Scholar 

  • Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Saltz L (2008) Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 20;26(12):2006–2012

    Article  CAS  Google Scholar 

  • Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, Zusman RM (1999) Use of sildenafil (Viagra) in patients with cardiovascular disease. Technology and Practice Executive Committee. Circulation 99(1):168–177

    CAS  PubMed  Google Scholar 

  • Chou TC (2006) Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 58:621–681

    Article  CAS  PubMed  Google Scholar 

  • Cohen M, Maritz F, Gensini GF, Danchin N, Timerman A, Huber K, Gurfinkel EP, White H, Fox KA, Vittori L, Le-Louer V, Bigonzi F (2000) The TETAMI trial: the safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and of tirofiban versus placebo in the treatment of acute myocardial infarction for patients not thrombolyzed: methods and design. Journal of Thrombosis and Thrombolysis 10(3):241–246

    Article  CAS  PubMed  Google Scholar 

  • Cohen M, Gensini GF, Maritz F, Gurfinkel EP, Huber K, Timerman A, Krzeminska-Pakula M, Danchin N, White HD, Santopinto J, Bigonzi F, Hecquet C, Vittori L; TETAMI Investigators (2003) The safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and tirofiban versus placebo in the treatment of acute ST-segment elevation myocardial infarction patients ineligible for reperfusion (TETAMI): a randomized trial. J Am Coll Cardiol 15:42, 8, 1348–1356

    Google Scholar 

  • D’Aquila RT, Hughes MD, Johnson VA, Fischl MA, Sommadossi JP, Liou SH, Timpone J, Myers M, Basgoz N, Niu M, Hirsch MS (1996) Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group Protocol 241 Investigators. Ann Intern Med 15;124(12):1019–30

    Google Scholar 

  • Danhof M, de Jongh J, De Lange EC, Della Pasqua OE, Ploeger BA, Voskuyl RA (2007) Mechanism-based pharmacokinetic-pharmacodynamic modeling: biophase distribution, receptor theory, and dynamical systems analysis. Annual Review of Pharmacology and Toxicology 47:357–400

    Article  CAS  PubMed  Google Scholar 

  • EMEA (1997) CPMP, Note for guidance on the investigation of drug interactions, CPMP/560/95

    Google Scholar 

  • EMEA (2002) CPMP, Note for guidance on clinical investigation of medicinal products in the treatment of diabetes mellitus, CPMP/EWP/1080/00

    Google Scholar 

  • EMEA (2004) CPMP, Note for guidance on clinical investigation of medicinal products in the treatment of hypertension, CPMP/EWP/238/95 Rev. 2

    Google Scholar 

  • Essig J, Belz GG, Wellstein A (1989) The assessment of ACE activity in man following angiotensin I challenges: a comparison of cilazapril, captopril and enalapril. British Journal of Clinical Pharmacology 27:217S–223S

    CAS  PubMed  Google Scholar 

  • FDA (2006) Guidance for industry, drug interaction studies – study design, data analysis, and implications for dosing and labeling sept. 2006

    Google Scholar 

  • FDA (2006) Guidance for industry fixed dose combinations, co-packaged drug products, and single-entity versions of previously approved antiretrovirals for the treatment of HIV

    Google Scholar 

  • FDA (2008) Guidance for industry, draft, guidance for industry, diabetes mellitus: developing drugs and therapeutic biologics for treatment and prevention

    Google Scholar 

  • Filitz J, Ihmsen H, Günther W, Tröster A, Schwilden H, Schüttler J, Koppert W (2008) Supra-additive effects of tramadol and acetaminophen in a human pain model. Pain 136(3):262–270

    Article  CAS  PubMed  Google Scholar 

  • Gessner PK (1995) Isobolographic analysis of interactions: an update on applications and utility. Toxicol 105:161–179

    Article  CAS  Google Scholar 

  • Goldberg AC, Sapre A, Liu J, Capece R, Mitchel YB; Ezetimibe Study Group (2004) Efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc 79(5):620–629

    Google Scholar 

  • Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, Anderson FH, Cooper C, Francis RM, Donaldson C, Gillespie WJ, Robinson CM, Torgerson DJ, Wallace WA; RECORD Trial Group (2005) Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet 7–13;365(9471):1621–1628

    Google Scholar 

  • Greco WR, Bravo O, Parsons JC (1995) The search for synergy: a critical review from a response surface perspective. Pharmacological Reviews 47:331–385

    CAS  PubMed  Google Scholar 

  • Haverkamp W, Breithardt G, Camm AJ, Janse MJ, Rosen MR, Antzelevitch C, Escande D, Franz M, Malik M, Moss A, Shah R (2000) The potential for QT prolongation and pro-arrhythmia by non-anti-arrhythmic drugs: clinical and regulatory implications. Cardiovascular Research 47(2):219–233

    Article  CAS  PubMed  Google Scholar 

  • ONTARGET Investigators, Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C (2008) Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 10;358(15):1547–1559

    Google Scholar 

  • Loewe S (1953) The problem of synergism and antagonism of combined drugs. Arzneimittelforsch 3:285–290

    CAS  PubMed  Google Scholar 

  • Loewe S, Muischnek H (1926) Über Kombinationswirkungen. Naunyn-Schmiedeberg’s Arch Pharmacol 114(5–6):313–326

    CAS  Google Scholar 

  • Lubsen J, Pocock SJ (1994) Factorial trials in cardiology: pros and cons. European Heart Journal 15:585–588

    CAS  PubMed  Google Scholar 

  • McAlister FA, Straus SE, Sackett DL, Altman DG (2003) Analysis and reporting of factorial trials: a systematic review. J Am Med Assoc 21;289(19):2545–2553

    Google Scholar 

  • Minto CF, Schnider TW, Short TG, Gregg KM, Gentilini A, Shafer SL (2000) Response surface model for anesthetic drug interactions. Anesthesiol 92:1603–1616

    Article  CAS  Google Scholar 

  • Montes A, Warner W, Puig MM (2000) Use of intravenous patient-controlled analgesia for the documentation of synergy between tramadol and metamizol. British Journal of Anaesthesia 85(2):217–223

    Article  CAS  PubMed  Google Scholar 

  • Nakornchai S, Konthiang P (2006) Activity of azithromycin or erythromycin in combination with antimalarial drugs against multidrug-resistant Plasmodium falciparum in vitro. Acta Tropica 100(3):185–191

    Article  CAS  PubMed  Google Scholar 

  • Parsley TL, Provonchee RB, Glicksman C, Zinner SH (1977) Synergistic activity of trimethoprim and amikacin against gram-negative bacilli. Antimicrobial Agents and Chemotherapy 12(3):349–352

    CAS  PubMed  Google Scholar 

  • Pöch G, Juan H (ed) (1985) In: Allgemeine pharmakodynamik. Thieme, Vol. 6. Wirkungen in Kombination, pp. 63–85

    Google Scholar 

  • Pordy RC (1994) Cilazapril plus hydrochlorothiazide: improved efficacy without reduced safety in mild to moderate hypertension. A double-blind placebo-controlled multicenter study of factorial design. Cardiology 85(5):311–322

    Article  CAS  PubMed  Google Scholar 

  • Robbins GK, De Gruttola V, Shafer RW, Smeaton LM, Snyder SW, Pettinelli C, Dubé MP, Fischl MA, Pollard RB, Delapenha R, Gedeon L, van der Horst C, Murphy RL, Becker MI, D’Aquila RT, Vella S, Merigan TC, Hirsch MS; AIDS Clinical Trials Group 384 Team (2003) Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med 11;349(24):2293–2303

    Google Scholar 

  • Ross EM, Kenakin TP (2001) Pharmacodynamics: mechanisms of drug action and the relationship between drug concentration and effect. In: Hardman JG, Limbird LE, Gilman AG (eds) Goodman and Gilman’s. The pharmacological basis of therapeutics, 10th edn. McGraw and Hill, New York

    Google Scholar 

  • Scheen AJ (2005) Drug interactions of clinical importance with antihyperglycaemic agents: an update. Drug Safety 28(7):601–631

    Article  CAS  PubMed  Google Scholar 

  • Schild HO (1947) pA, a new scale for the measurement of drug antagonism. Br J Pharmacol 2:189–206

    CAS  Google Scholar 

  • Scholze J, Breitstadt A, Cairns V, Bauer B, Bender N, Priestley C, Moreadith C, Phillips J, Vander Elst E, Koch G (1993) Short report: ramipril and hydrochlorothiazide combination therapy in hypertension: a clinical trial of factorial design. The East Germany Collaborative Trial Group. Journal of Hypertension 11(2):217–221

    Article  CAS  PubMed  Google Scholar 

  • Seymour RM, Routledege PA (1998) Important drug–drug interactions in the elderly. Drugs and Aging 12(6):485–494

    Article  CAS  PubMed  Google Scholar 

  • Tallarida RJ (2001) Drug synergism: its detection and applications. The Journal of Pharmacology and Experimental Therapeutics 298(3):865–872

    CAS  PubMed  Google Scholar 

  • Tallarida RJ (2006) An overview of drug combination analysis with isobolograms. The Journal of Pharmacology and Experimental Therapeutics 319(1):1–7

    Article  CAS  PubMed  Google Scholar 

  • Trujillo TC, Nolan PE (2000) Antiarrhythmic agents: drug interactions of clinical significance. Drug Safety 23(6):509–532

    Article  CAS  PubMed  Google Scholar 

  • Wellstein A, Palm D, Pitschner HF, Belz GG (1985) Receptor binding of propranolol is the missing link between plasma concentrations kinetics and effect–time course in man. European Journal of Clinical Pharmacology 29:131–147

    Article  CAS  PubMed  Google Scholar 

  • Wellstein A, Essig J, Belz GG (1987) Inhibition of angiotensin-I response by cilazapril and its time course in normal volunteers. Clinical Pharmacology and Therapeutics 41:639–644

    Article  CAS  PubMed  Google Scholar 

  • Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 20;342(3):145–153. Erratum in: 4;342(18):1376, N Engl J Med 2000

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hochschule Fresenius, Limburger Str. 2, 65510, Idstein, Germany

    Markus Hinder

Authors
  1. Markus Hinder
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Markus Hinder .

Editor information

Editors and Affiliations

  1. Bohl Str. 28, 73430, Aalen, Germany

    Hans Gerhard Vogel

  2. Sanofi Aventis Deutschland GmbH, Industriepark Hoechst, Building G877, R&D Metabolism and PK Germany, 65926, Frankfurt am Main, Germany

    Jochen Maas

  3. Merz Pharmaceuticals GmbH, Eckenheimer Landstraβe 100, 60318, Frankfurt am Main, Germany

    Alexander Gebauer

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this entry

Cite this entry

Hinder, M. (2011). Pharmacodynamic Drug–Drug Interactions. In: Vogel, H.G., Maas, J., Gebauer, A. (eds) Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-89891-7_29

Download citation

Publish with us

Policies and ethics

Search

Navigation