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 |

isoniazid

  • isoniazid is a weak inhibitor of CYP3A.
  • isoniazid did not meet the criteria of being an inhibitor or inducer of CYP2C19.
  • isoniazid has not been evaluated in the literature showing its role of altering the activities of CYP2C9.
  • CYP2C9CYP2C19CYP3A
    Weak inhibitorsamiodarone [1]
    cimetidine [2]
    co-trimoxazole [3]
    disulfiram [4]
    echinacea [5]
    fluvastatin [6]
    fluvoxamine [7]
    ketoconazole [8]
    lovastatin [1]
    metronidazole [9]
    sertraline [10]
    simvastatin [1]
    sulfadiazine [11]
    voriconazole [12]
    zafirlukast [a]
    finasteride [13]
    interferon alpha-2b [14]
    ketoconazole [15]
    omeprazole [16]
    oral contraceptives [17]
    roxithromycin [18]
    alprazolam [19]
    amiodarone [20]
    aspirin [21]
    azithromycin [22]
    bicalutamide [23]
    cimetidine [24]
    co-trimoxazole [25]
    cyclosporine [26]
    fluvoxamine [27]
    isoniazid [28]
    maraviroc [29]
    oral contraceptives [30]
    ranitidine [31]
    roxithromycin [32]
    simvastatin [33]
    Criteria not metcapecitabine [34]
    itraconazole [35]
    carbamazepine [36]
    cimetidine [37]
    isoniazid [38]
    lansoprazole [39]
    pantoprazole [40]
    propoxyphene [41]
    rabeprazole [42]
    amprenavir [b]
    buspirone [b]
    ciprofloxacin [c] [43]
    citalopram [b]
    darifenacin [b]
    darunavir/ritonavir [c] [b]
    dasatinib [b]
    efavirenze
    erlotinib [b]
    fosamprenavir [c] [44]
    nevirapine [b]
    nilotinib [b]
    omeprazole [b]
    oxcarbazepine [b]
    phenobarbitone [d] [45]
    propoxyphene [46]
    rifabutin [b]
    Not evaluated in the literatureatazanavir
    efavirenz
    5-fluorouracil
    fluoxetine
    imatinib
    isoniazid
    leflunomide
    phenobarbitone
    phenytoin
    ritonavir
    teniposide
    efavirenz [e]
    indomethacin
    modafinil
    oxcarbazepine
    phenobarbitone
    phenytoin
    prednisone
    anastrozole
    atenolol
    atorvastatin
    caffeine
    cyproterone
    ethosuximide
    danazol
    delavirdine [c]
    digoxin
    gemfibrozil
    lapatinib
    metoprolol
    metronidazole
    mifepristone
    norfloxacin
    quinipristin-dalfopristin
    raloxifene
    repaglinide
    valproate

    Footnotes and References

    a.assessment based on product information accessed via the Therapeutic Goods Administration of Australia Product and Consumer Medicines Information website ( https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=PI&q=&r=https://www.ebs.tga.gov.au/ ).
    b.clinical PK interaction studies referred to in product information.
    c.likely to be a major inhibitor based on subjective evaluation (≥ 2-fold AUC increase or ≥ 50% decrease in clearance of in vivo CYP probe).
    d.likely to be a major inducer based on subjective evaluation (≥ 2-fold decrease in AUC or ≥ 50% increase in clearance of in vivo CYP probe).
    e.poster found at http://www.klinikum.uni-heidelberg.de/fileadmin/medizinische_klinik/Abteilung_6/pdf/Posterpreis_VKliPha2008_Bayer.pdf
    1.Herman D, Locatelli I, Grabnar I, Peternel P, Stegnar M, Lainscak M, Mrhar A, Breskvar K, Dolzan V. The influence of co-treatment with carbamazepine, amiodarone and statins on warfarin metabolism and maintenance dose. European Journal of Clinical Pharmacology 2006; 62: 291-96.[PubMed]
    2.Back DJ, Tjia J, Monig H, Ohnhaus EE, Park BK. Selective inhibition of drug oxidation after simultaneous administration of two probe drugs, antipyrine and tolbutamide. European Journal of Clinical Pharmacology 1988; 34: 157-63.[PubMed]
    3.Miners JO, Wing LMH. Selective inhibition of drug oxidation after simultaneous administration of two probe drugs, antipyrine and tolbutamide. British Journal of Clinical Pharmacology 1985; 20: 482-85.[PubMed]
    4.Svendsen TL, Kristensen MB, Hansen JM, Skovsted L. The influence of disulfiram on the half life and metabolic clearance rate of diphenylhydantoin and tolbtamide in man. European Journal of Clinical Pharmacology 1976; 5-6: 439-41.[PubMed]
    5.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]
    6.Kim MJ, Nafziger AN, Kashuba ADM, Kirchheiner J, Bauer S, Gaedigk A, Bertino JS. Effects of fluvastatin and cigarette smoking on CYP2C9 activity measured using the probe S-warfarin. European Journal of Clinical Pharmacology 2006; 62: 431-36.[PubMed]
    7.Madsen H, Enggaard TP, Hansen LL, Klitgaard NA, Brosen K. Fluvoxamine inhibits the CYP2C9 catalyzed biotransformation of tolbutamide. Clinical Pharmacology & Therapeutics 2001; 69: 41-47.[PubMed]
    8.Krishnaiah YSR, Satyanarayana S, Visweswaram D. Interaction between tolbutamide and ketoconazole in healthy subjects. British Journal of Clinical Pharmacology 1994; 37: 205-07.[PubMed]
    9.O'Reilly R. The stereoselective interaction of warfarin and metronidazole in man. New England Journal of Medicine 1976; 295: 354-57.[PubMed]
    10.Tremaine LM, Wilner KD, Preskorn SH. A study of the potential effect of sertraline on the pharmacokinetics and protein binding of tolbutamide. Clinical Pharmacokinetics 1997; 32: 31-36.[PubMed]
    11.Hansen JM, Kampmann JP, Siersbaeknielsen K, Lumholtz IB, Arroe M, Abildgaard U, Skovsted L. The effect of different sulfonamides on phenytoin metabolism in man. Acta Medica Scandinavica 1979: 106-10.[PubMed]
    12.Purkins L, Wood N, Ghahramani P, Love ER, Eve MD, Fielding A. Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration. British Journal of Clinical Pharmacology 2003; 56: 37-44.[PubMed]
    13.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]
    14.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]
    15.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]
    16.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]
    17.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]
    18.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]
    19.Buch AB, Van Harken DR, Seidehamel RJ, Barbhaiya RH. A study of pharmacokinetic interaction between buspirone and alprazolam at steady state. Journal of Clinical Pharmacology 1993; 33: 1104-09.[PubMed]
    20.Becquemont L, Neuvonen M, Verstuyft C, Jaillon P, Letierce A, Neuvonen PJ, Funck-Brentano C. Amiodarone interacts with simvastatin but not with pravastatin disposition kinetics. Clinical Pharmacology & Therapeutics 2007; 81: 679-84.[PubMed]
    21.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]
    22.Zimmermann T, Yeates RA, Laufen H, Scharpf F, Leitold M, Wildfeuer A. Influence of the antibiotics erythromycin and azithromycin on the pharmacokinetics and pharmacodynamics of midazolam. Arzneimittel-Forschung/Drug Research 1996; 46: 213-17.[PubMed]
    23.Cockshott ID. Bicalutamide - Clinical pharmacokinetics and metabolism. Clinical Pharmacokinetics 2004; 43: 855-78.[PubMed]
    24.Somogyi A, Muirhead M. Pharmacokinetic Interactions of Cimetidine 1987. Clinical Pharmacokinetics 1987; 12: 321-66.[PubMed]
    25.Abel S, Russell D, Whitlock LA, Ridgway CE, Muirhead GJ. The effects of cotrimoxazole or tenofovir co-administration on the pharmacokinetics of maraviroc in healthy volunteers. British Journal of Clinical Pharmacology 2008; 65: 47-53.[PubMed]
    26.Li G, Treiber G, Meinshausen J, Wolf J, Werringloer J, Klotz U. Is cyclosporin A an inhibitor of drug metabolism? British Journal of Clinical Pharmacology 1990; 30: 71-77.[PubMed]
    27.Lam YWF, Alfaro CL, Ereshefsky L, Miller M. Pharmacokinetic and pharmacodynamic interactions of oral midazolam with ketoconazole, fluoxetine, fluvoxamine, and nefazodone. Journal of Clinical Pharmacology 2003; 43: 1274-82.[PubMed]
    28.Ochs HR, Greenblatt DJ, Knuchel M. Differential effect of isoniazid on triazolam oxidation and oxazepam conjugation. British Journal of Clinical Pharmacology 1983; 16: 743-46.[PubMed]
    29.Abel S, Russell D, Whitlock LA, Ridgway CE, Muirhead GJ. Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinyloestradiol/levonorgestrel in healthy volunteers. British Journal of Clinical Pharmacology 2008; 65: 19-26.[PubMed]
    30.Palovaara S, Kivisto KT, Tapanainen P, Manninen P, Neuvonen PJ, Laine K. Effect of an oral contraceptive preparation containing ethinylestradiol and gestodene on CYP3A4 activity as measured by midazolam 1 '-hydroxylation. British Journal of Clinical Pharmacology 2000; 50: 333-37.[PubMed]
    31.Elliott P, Dundee JW, Elwood RJ, Collier PS. The influence of H2 receptor antagonists on the plasma concentrations of midazolam and temazepam. European Journal of Anaesthesiology 1984; 1: 245-51.[PubMed]
    32.Backman JT, Aranko K, Himberg JJ, Olkkola KT. A pharmacokinetic interaction between roxithromycin and midazolam. European Journal of Clinical Pharmacology 1994; 46: 551-55.[PubMed]
    33.Prueksaritanont T, Vega JM, Zhao J, Gagliano K, Kuznetsova O, Musser B, Amin RD, Liu L, Roadcap BA, Dilzer S, Lasseter KC, Rogers JD. Interactions between simvastatin and troglitazone or pioglitazone in healthy subjects. Journal of Clinical Pharmacology 2001; 41: 573-81.[PubMed]
    34.Camidge R, Reigner B, Cassidy J, Grange S, Abt M, Weidekamm E, Jodrell D. Significant effect of capecitabine on the pharmacokinetics and pharmacodynamics of warfarin in patients with cancer. Journal of Clinical Oncology 2005; 23: 4719-25.[PubMed]
    35.Kivisto KT, Kantola T, Neuvonen PJ. Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. British Journal of Clinical Pharmacology 1998; 46: 49-53.[PubMed]
    36.Bertilsson L, Tybring G, Widen J, Chang M, Tomson T. Carbamazepine treatment induces the CYP3A4 catalysed sulphoxidation of omeprazole, but has no or less effect on hydroxylation via CYP2C19. British Journal of Clinical Pharmacology 1997; 44: 186-89.[PubMed]
    37.Gough PA, Curry SH, Araujo OE, Robinson JD, Dallman JJ. Influence of cimetidine on oral diazepam elimination with measurement of subsequent cognitive change. British Journal of Clinical Pharmacology 1982; 14: 739-42.[PubMed]
    38.Ochs HR, Greenblatt DJ, Roberts GM, Dengler HJ. Diazepam interaction with antituberculosis drugs. Clinical Pharmacology & Therapeutics 1981; 29: 671-78.[PubMed]
    39.Lefebvre RA, Flouvat B, Karolactamisier S, Moerman E, Vanganse E. Influence of lansoprazole treatment on diazepam plasma concentrations. Clinical Pharmacology & Therapeutics 1992; 52: 458-63.[PubMed]
    40.Gugler R, Hartmann M, Rudi J, Brod I, Huber R, Steinijans VW, Bliesath H, Wurst W, Klotz U. Lack of pharmacokinetic interaction of pantoprazole with diazepam in man. British Journal of Clinical Pharmacology 1996; 42: 249-52.[PubMed]
    41.Sanz EJ, Bertilsson L. d-Propoxyphene is a potent inhibitor of debrisoquine, but not S-mephenytoin 4-hydroxylation in vivo. Therapeutic Drug Monitoring 1990; 12: 297-99.[PubMed]
    42.Ishizaki T, Chiba K, Manabe K, Koyama E, Hayashi M, Yasuda S, Horai Y, Tomono Y, Yamato C, Toyoki T. Comparison of the interaction potential of a new proton pump inhibitor, E3810, versus omeprazole with diazepam in extensive and poor metabolizers of S-mephenytoin 4'-hydroxylation. Clinical Pharmacology & Therapeutics 1995; 58: 155-64.[PubMed]
    43.Hedaya MA, El-Afify DR, El-Maghraby GM. The effect of ciprofloxacin and clarithromycin on sildenafil oral bioavailability in human volunteers. Biopharmaceutics & Drug Disposition 2006; 27: 103-10.[PubMed]
    44.Wire MB, Shelton MJ, Studenberg S. Fosamprenavir - Clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clinical Pharmacokinetics 2006; 45: 137-68.[PubMed]
    45.Schellens JHM, Vanderwart JHF, Brugman M, Breimer DD. Influence of enzyme induction and inhibition on the oxidation of nifedipine, sparteine, mephenytoin and antipyrine in humans as assessed by a "cocktail" study design. Journal of Pharmacology and Experimental Therapeutics 1989; 249: 638-45.[PubMed]
    46.Abernethy DR, Greenblatt DJ, Morse DS, Shader RI. Interaction of propoxyphene with diazepam, alprazolam and lorazepam. British Journal of Clinical Pharmacology 1985; 19: 51-54.[PubMed]
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