PKIS v2.0 A clinical tool for identifying important pharmacokinetic drug-drug interactions
| 1. Accepted major perpetrators | 2. Rejected perpetrators | 3. Unclassifiable | 4. Full table |

ticlopidine

  • ticlopidine is a strong inhibitor of CYP2C19.
  • ticlopidine is a weak inhibitor of CYP1A2.
  • ticlopidine has not been evaluated in the literature showing its role of altering the activities of CYP2D6.
  • CYP1A2CYP2C19CYP2D6
    Strong inhibitorsciprofloxacin [1]
    fluvoxamine [2]
    fluconazole [3]
    fluvoxamine [4]
    ticlopidine [5]
    bupropion [6]
    fluoxetine [7]
    paroxetine [8]
    perhexaline [9]
    Weak inhibitorscimetidine [10]
    clarithromycin [11]
    diltiazem [12]
    echinacea [13]
    erythromycin [11]
    mexiletine [14]
    moclobemide [15]
    norfloxacin [16]
    propranolol [17]
    roxithromycin [11]
    ticlopidine [18]
    verapamil [19]
    finasteride [20]
    interferon alpha-2b [21]
    ketoconazole [22]
    omeprazole [23]
    oral contraceptives [24]
    roxithromycin [25]
    amiodarone [26]
    amitriptyline [27]
    aspirin [28]
    celecoxib [29]
    cimetidine [30]
    darifenacin [a]
    desvenlafaxine [31]
    diltiazem [32]
    diphenhydramine [33]
    escitalopram [34]
    felodipine [35]
    fluvoxamine [36]
    gefitinib [37]
    hydralazine [38]
    imatinib [39]
    interferon alpha-2b [21]
    ketoconazole [40]
    methadone [41]
    metoprolol [42]
    nortriptyline [43]
    oral contraceptives [44]
    oxprenolol [42]
    pindolol [42]
    propranolol [42]
    ranitidine [45]
    risperidone [46]
    ritonavir [47]
    saw palmetto [48]
    sertraline [8]
    timolol [42]
    venlafaxine [49]
    Not evaluated in the literatureatazanavir
    insulin
    modafinil
    efavirenz [b]
    indomethacin
    modafinil
    oxcarbazepine
    phenobarbitone
    phenytoin
    prednisone
    artemether/ lumefantrine
    chlorpheniramine
    chlorpromazine
    cocaine
    doxorubicin
    haloperidol
    ibuprofen
    methadone
    metoclopramide
    nilotinib
    ticlopidine

    Footnotes and References

    a.systemic preparations not available in Australia or New Zealand.
    b.poster found at http://www.klinikum.uni-heidelberg.de/fileadmin/medizinische_klinik/Abteilung_6/pdf/Posterpreis_VKliPha2008_Bayer.pdf
    1.Granfors MT, Backman JT, Neuvonen M, Neuvonen PJ. Ciprofloxacin greatly increases concentrations and cypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism. Clinical Pharmacology & Therapeutics 2004; 76: 598-606.[PubMed]
    2.Granfors MT, Backman JT, Neuvonen M, Ahonen J, Neuvonen PJ. Fluvoxamine Drastically Increases Concentrations and Effects of Tizanidine: A Potentially Hazardous Interaction. Clinical Pharmacology & Therapeutics 2004; 75: 331-41.[PubMed]
    3.Kang BC, Yang CQ, Cho HK, Suh OK, Shin WG. Influence of fluconazole on the pharmacokinetics of omeprazole in healthy volunteers. Biopharmaceutics & Drug Disposition 2002; 23: 77-81.[PubMed]
    4.Yasui-Furukori N, Takahata T, Nakagami T, Yoshiya G, Inoue Y, Kaneko S, Tateishi T. Different inhibitory effect of fluvoxamine on omeprazole metabolism between CYP2C19 genotypes. British Journal of Clinical Pharmacology 2004; 57: 487-94.[PubMed]
    5.Ieiri I, Kimura M, He S, Urae A, Otsubo K, Ishizaki T. Interaction magnitude, pharmacokinetics and pharmacodynamics of ticlopidine in relation to CYP2C19 genotypic status. Pharmacogenetics and Genomics 2005; 15: 851-59.[PubMed]
    6.Kotlyar M, Brauer LH, Tracy TS, Hatsukami DK, Harris J, Bronars CA, Adson DE. Inhibition of CYP2D6 activity by bupropion. Journal of Clinical Psychopharmacology 2005; 25: 226-29.[PubMed]
    7.Bergstrom RF, Peyton AL, Lemberger L. Quantification and mechanism of the fluoexetine and tricyclic antidepressant interaction. Clinical Pharmacology & Therapeutics 1992; 51: 239-48.[PubMed]
    8.Alderman J, Preskorn SH, Greenblatt DJ, Harrison W, Penenberg D, Allison J, Chung M. Desipramine pharmacokinetics when coadministered with paroxetine or sertraline in extensive metabolizers. Journal of Clinical Psychopharmacology 1997; 17: 284-91.[PubMed]
    9.Davies BJL, Coller JK, James HM, Gillis D, Somogyi AA, Horowitz JD, Morris RG, Sallustio BC. Clinical inhibition of CYP2D6-catalysed metabolism by the antianginal agent perhexiline. British Journal of Clinical Pharmacology 2004; 57: 456-63.[PubMed]
    10.Naline E, Sanceaume M, Pays M, Advenier C. Application of theophylline metabolite assays to the exploration of liver microsome oxidative function in man. Fundamental & Clinical Pharmacology 1988; 2: 341-51.[PubMed]
    11.Periti P, Mazzei T, Mini E, Novelli A. Pharmacokinetic drug-interactions of macrolides. Clinical Pharmacokinetics 1992; 23: 106-31.[PubMed]
    12.Soto J, Sacristan JA, Alsar MJ. Diltiazem Treatment Impairs Theophylline Elimination in Patients with Bronchospastic Airway Disease. Therapeutic Drug Monitoring 1994; 16: 49-52.[PubMed]
    13.Gorski JC, Huang SM, Pinto A, Hamman MA, Hilligoss JK, Zaheer NA, Desai M, Miller M, Hall SD. The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo. Clinical Pharmacology & Therapeutics 2004; 75: 89-100.[PubMed]
    14.Hurwitz A, Vacek JL, Botteron GW, Sztern MI, Hughes EM, Jayaraj A. Mexiletine effects on theophylline disposition Clinical Pharmacology & Therapeutics 1991; 50: 299-307.[PubMed]
    15.Gram LF, Guentert TW, Grange S, Vistisen K, Brosen K. Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6, and CYP1A2 - a panel study. Clinical Pharmacology & Therapeutics 1995; 57: 670-77.[PubMed]
    16.Ho G, Tierney MG, Dales RE. Evaluation of the effect of norfloxacin on the pharmacokinetics of theophylline. Clinical Pharmacology & Therapeutics 1988; 44: 35-38.[PubMed]
    17.Miners JO, Wing LMH, Lillywhite KJ, Robson RA. Selectivity and dose-dependency of the inhibitory effect of propranolol on theophylline metabolism in man. British Journal of Clinical Pharmacology 1985; 20: 219-23.[PubMed]
    18.Colli A, Buccino G, Cocciolo M, Parravicini R, Elli GM, Scaltrini G. Ticlopidine-theophylline interaction. Clinical Pharmacology & Therapeutics 1987; 41: 358-62.[PubMed]
    19.Stringer KA, Mallet J, Clarke M, Lindenfeld JA. The effect of three different oral doses of verapamil on the disposition of theophylline. European Journal of Clinical Pharmacology 1992; 43: 35-38.[PubMed]
    20.Yasumori T, Narita H, Matsuda T, Takubo T, Ogawa M, Ishii M, Hara K, Ishii Y, Okuyama K, Fujimoto G, Ochiai H, Kano A, Hasegawa S, Sato K, Taniguchi T. Finasteride 1 mg has no inhibitory effect on omeprazole metabolism in extensive and poor metabolizers for CYP2C19 in Japanese. European Journal of Clinical Pharmacology 2006; 62: 939-46.[PubMed]
    21.Islam M, Frye RF, Richards TJ, Sbeitan I, Donnelly SS, Glue P, Agarwala SS, Kirkwood JM. Differential Effect of IFNalpha-2b on the Cytochrome P450 Enzyme System: A Potential Basis of IFN Toxicity and Its Modulation by Other Drugs. Clinical Cancer Research 2002; 8: 2480-87.[PubMed]
    22.Bottiger Y, Tybring G, Gotharson E, Bertilsson L. Inhibition of the sulfoxidation of omeprazole by ketoconazole in poor and extensive metabolizers of S-mephenytoin. Clinical Pharmacology & Therapeutics 1997; 62: 384-91.[PubMed]
    23.Caraco Y, Wilkinson GR, Wood AJJ. Differences between white subjects and Chinese subjects in the in vivo inhibition of cytochrome P450s 2C19, 2D6, and 3A by omeprazole. Clinical Pharmacology & Therapeutics 1996; 60: 396-404.[PubMed]
    24.Laine K, Tybring G, Bertilsson L. No sex-related differences but significant inhibition by oral contraceptives of CYP2C19 activity as measured by the probe drugs mephenytoin and omeprazole in healthy Swedish white subjects. Clinical Pharmacology & Therapeutics 2000; 68: 151-59.[PubMed]
    25.Kees F, Holstege A, Ittner KP, Zimmermann M, Lock G, Scholmerich J, Grobecker H. Pharmacokinetic interaction between proton pump inhibitors and roxithromycin in volunteers. Alimentary Pharmacology & Therapeutics 2000; 14: 407-12.[PubMed]
    26.Fukumoto K, Kobayashi T, Tachibana K, Kat R, Tanaka K, Komamura K, Kamakura S, Kitakaze M, Ueno K. Effect of amiodarone on the serum concentration/dose ratio of metoprolol in patients with cardiac arrhythmia. Drug Metab Pharmacokinet 2006; 21: 501-05.[PubMed]
    27.Baumann P, Meyer JW, Amey M, Baettig D, Bryois C, Jonzierperey M, Koeb L, Monney C, Woggon B. Dextromethorphan and mephenytoin phenotyping of patients treated with thioridazine or amitriptyline. Therapeutic Drug Monitoring 1992; 14: 1-8.[PubMed]
    28.Chen XP, Tan ZR, Huang SL, Huang Z, Ou-Yang DS, Zhou HH. Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects. Clinical Pharmacology & Therapeutics 2003; 73: 264-71.[PubMed]
    29.Werner U, Werner D, Rau T, Fromm MF, Hinz B, Brune K. Celecoxib inhibits metabolism of cytochrome P450 2D6 substrate metoprolol in humans. Clinical Pharmacology & Therapeutics 2003; 74: 130-37.[PubMed]
    30.Steiner E, Spina E. Differences in the inhibitory effect of cimetidine on desipramine metabolism between rapid and slow debrisoquin hydroxylators. Clinical Pharmacology & Therapeutics 1987; 42: 278-82.[PubMed]
    31.Patroneva A, Connolly SM, Fatato P, Pedersen R, Jiang Q, Paul J, Guico-Pabia C, Isler JA, Burczynski ME, Nichols AI. An Assessment of Drug-Drug Interactions: The Effect of Desvenlafaxine and Duloxetine on the Pharmacokinetics of the CYP2D6 Probe Desipramine in Healthy Subjects. Drug Metabolism and Disposition 2008; 36: 2484-91.[PubMed]
    32.Tateishi T, Nakashima H, Shitou T, Kumagai Y, Ohashi K, Hosoda S, Ebihara A. Effect of diltiazem on the pharmacokinetics of propranolol, metoprolol and atenolol. European Journal of Clinical Pharmacology 1989; 36: 67-70.[PubMed]
    33.Sharma A, Pibarot P, Pilote S, Dumesnil JG, Arsenault M, Belanger PM, Meibohm B, Hamelin BA. Modulation of metoprolol pharmacokinetics and hemodynamics by diphenhydramine coadministration during exercise testing in healthy premenopausal women. Journal of Pharmacology and Experimental Therapeutics 2005; 313: 1172-81.[PubMed]
    34.Preskorn SH, Greenblatt DJ, Flockhart D, Luo Y, Perloff ES, Harmatz JS, Baker B, Klick-Davis A, Desta Z, Burt T. Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers. Journal of Clinical Psychopharmacology 2007; 27: 28-34.[PubMed]
    35.Smith SR, Wilkins MR, Jack DB, Kendall MJ, Laugher S. Pharmacokinetic interactions between felodipine and metoprolol. European Journal of Clinical Pharmacology 1987; 31: 575-78.[PubMed]
    36.Alfaro CL, Lam YWF, Simpson J, Ereshefsky L. CYP2D6 status of extensive metabolizers after multiple-dose fluoxetine, fluvoxamine, paroxetine, or sertraline. Journal of Clinical Psychopharmacology 1999; 19: 155-63.[PubMed]
    37.Swaisland HC, Ranson M, Smith RP, Leadbetter J, Laight A, McKillop D, Wild MJ. Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol. Clinical Pharmacokinetics 2005; 44: 1067-81.[PubMed]
    38.Jack DB, Kendall MJ, Dean S, Laugher SJ, Zaman R, Tenneson ME. The effect of hydralazine on the pharmacokinetics of three different beta adrenoceptor antagonists: metoprolol, nadolol, and acebutolol. Biopharmaceutics & Drug Disposition 1982; 3: 47-54.[PubMed]
    39.Wang YF, Zhou L, Dutreix C, Leroy E, Yin Q, Sethuraman V, Riviere GJ, Yin OQP, Schran H, Shen ZX. Effects of imatinib (Glivec) on the pharmacokinetics of metoprolol, a CYP2D6 substrate, in Chinese patients with chronic myelogenous leukaemia. British Journal of Clinical Pharmacology 2008; 65: 885-92.[PubMed]
    40.Atiba JO, Blaschke TF, Wilkinson GR. Effects of ketoconazole on the polymorphic 4-hydroxylations of S-mephenytoin and debrisoquine. British Journal of Clinical Pharmacology 1989; 28: 161-65.[PubMed]
    41.Wu D, Otton SV, Sproule BA, Busto U, Inaba T, Kalow W, Sellers EM. Inhibition of human cytochrome P450 2D6 (CYP2D6) by methadone. British Journal of Clinical Pharmacology 1993; 35: 30-34.[PubMed]
    42.Kallio J, Huupponen R, Seppala M, Sako E, Iisalo E. The effects of beta-adrenoceptor antagonists and levomepromazine on the metabolic ratio of debrisoquine. British Journal of Clinical Pharmacology 1990; 30: 638-43.[PubMed]
    43.Solai LK, Pollock BG, Mulsant BH, Frye RF, Miller MD, Sweet RA, Kirshner M, Sorisio D, Begley A, Reynolds CF. Effect of nortriptyline and paroxetine on CYP2D6 activity in depressed elderly patients. Journal of Clinical Psychopharmacology 2002; 22: 481-86.[PubMed]
    44.Kendall MJ, Quarterman CP, Jack DB, Beeley L. Metoprolol pharmacokinetics and the oral contraceptive pill. British Journal of Clinical Pharmacology 1982; 14: 120-22.[PubMed]
    45.Kelly JG, Salem SAM, Kinney CD, Shanks RG, McDevitt DG. Effects of ranitidine on the disposition of metoprolol. British Journal of Clinical Pharmacology 1985; 19: 219-24.[PubMed]
    46.Eap CB, Bondolfi G, Zullino D, Bryois C, Fuciec M, Savary L, Jonzier-Perey M, Baumann P. Pharmacokinetic drug interaction potential of risperidone with cytochrome P450 isozymes as assessed by the dextromethorphan, the caffeine, and the mephenytoin test. Therapeutic Drug Monitoring 2001; 23: 228-31.[PubMed]
    47.Aarnoutse RE, Kleinnijenhuis J, Koopmans PP, Touw DJ, Wieling J, Hekster YA, Burger DM. Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers. Clinical Pharmacology & Therapeutics 2005; 78: 664-74.[PubMed]
    48.Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang JS, Chavin KD. Multiple doses of saw palmetto (Serenoa repens) did not alter cytochrome P450 2D6 and 3A4 activity in normal volunteers. Clinical Pharmacology & Therapeutics 2003; 74: 536-42.[PubMed]
    49.Amchin J, Ereshefsky L, Zarycranski W, Taylor K, Albano D, Klockowski PM. Effect of venlafaxine versus fluoxetine on metabolism of dextromethorphan, a CYP2D6 probe. Journal of Clinical Pharmacology 2001; 41: 443-51.[PubMed]
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