Isoniazid: Uses, Interactions, Mechanism of Action | DrugBank Online

Step 2

FDA Approved Drug Products: RIFATER (rifampin, isoniazid and pyrazinamide USP) tablets (February 2023) [Link]

Step 3

Pym AS, Domenech P, Honore N, Song J, Deretic V, Cole ST: Regulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity and virulence by furA of Mycobacterium tuberculosis. Mol Microbiol. 2001 May;40(4):879-89. [Article] Heym B, Alzari PM, Honore N, Cole ST: Missense mutations in the catalase-peroxidase gene, katG, are associated with isoniazid resistance in Mycobacterium tuberculosis. Mol Microbiol. 1995 Jan;15(2):235-45. [Article] Wilson TM, de Lisle GW, Collins DM: Effect of inhA and katG on isoniazid resistance and virulence of Mycobacterium bovis. Mol Microbiol. 1995 Mar;15(6):1009-15. [Article] Vilcheze C, Jacobs WR Jr: The mechanism of isoniazid killing: clarity through the scope of genetics. Annu Rev Microbiol. 2007;61:35-50. [Article]

Step 4

Schroeder EK, Basso LA, Santos DS, de Souza ON: Molecular dynamics simulation studies of the wild-type, I21V, and I16T mutants of isoniazid-resistant Mycobacterium tuberculosis enoyl reductase (InhA) in complex with NADH: toward the understanding of NADH-InhA different affinities. Biophys J. 2005 Aug;89(2):876-84. Epub 2005 May 20. [Article] Wilson TM, de Lisle GW, Collins DM: Effect of inhA and katG on isoniazid resistance and virulence of Mycobacterium bovis. Mol Microbiol. 1995 Mar;15(6):1009-15. [Article] Broussy S, Coppel Y, Nguyen M, Bernadou J, Meunier B: 1H and 13C NMR characterization of hemiamidal isoniazid-NAD(H) adducts as possible inhibitors of InhA reductase of Mycobacterium tuberculosis. Chemistry. 2003 May 9;9(9):2034-8. [Article] Vilcheze C, Jacobs WR Jr: The mechanism of isoniazid killing: clarity through the scope of genetics. Annu Rev Microbiol. 2007;61:35-50. [Article] Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Step 5

Fontana E, Dansette PM, Poli SM: Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity. Curr Drug Metab. 2005 Oct;6(5):413-54. [Article]

Step 6

Fontana E, Dansette PM, Poli SM: Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity. Curr Drug Metab. 2005 Oct;6(5):413-54. [Article]

Step 7

Fontana E, Dansette PM, Poli SM: Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity. Curr Drug Metab. 2005 Oct;6(5):413-54. [Article]

Step 8

Fontana E, Dansette PM, Poli SM: Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity. Curr Drug Metab. 2005 Oct;6(5):413-54. [Article]

Step 9

Wang F, Jain P, Gulten G, Liu Z, Feng Y, Ganesula K, Motiwala AS, Ioerger TR, Alland D, Vilcheze C, Jacobs WR Jr, Sacchettini JC: Mycobacterium tuberculosis dihydrofolate reductase is not a target relevant to the antitubercular activity of isoniazid. Antimicrob Agents Chemother. 2010 Sep;54(9):3776-82. doi: 10.1128/AAC.00453-10. Epub 2010 Jun 21. [Article]

Step 10

Upton AM, Mushtaq A, Victor TC, Sampson SL, Sandy J, Smith DM, van Helden PV, Sim E: Arylamine N-acetyltransferase of Mycobacterium tuberculosis is a polymorphic enzyme and a site of isoniazid metabolism. Mol Microbiol. 2001 Oct;42(2):309-17. [Article]

Step 11

Upton AM, Mushtaq A, Victor TC, Sampson SL, Sandy J, Smith DM, van Helden PV, Sim E: Arylamine N-acetyltransferase of Mycobacterium tuberculosis is a polymorphic enzyme and a site of isoniazid metabolism. Mol Microbiol. 2001 Oct;42(2):309-17. [Article]

Step 12

Wen X, Wang JS, Neuvonen PJ, Backman JT: Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes. Eur J Clin Pharmacol. 2002 Jan;57(11):799-804. [Article] Nishimura Y, Kurata N, Sakurai E, Yasuhara H: Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities. J Pharmacol Sci. 2004 Nov;96(3):293-300. Epub 2004 Nov 5. [Article] Court MH, Almutairi FE, Greenblatt DJ, Hazarika S, Sheng H, Klein K, Zanger UM, Bourgea J, Patten CJ, Kwara A: Isoniazid mediates the CYP2B6*6 genotype-dependent interaction between efavirenz and antituberculosis drug therapy through mechanism-based inactivation of CYP2A6. Antimicrob Agents Chemother. 2014 Jul;58(7):4145-52. doi: 10.1128/AAC.02532-14. Epub 2014 May 12. [Article] Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L56). Canadian Pharmacists Association. [ISBN:1-894402-22-7]

Step 13

Polasek TM, Elliot DJ, Lewis BC, Miners JO: Mechanism-based inactivation of human cytochrome P4502C8 by drugs in vitro. J Pharmacol Exp Ther. 2004 Dec;311(3):996-1007. doi: 10.1124/jpet.104.071803. Epub 2004 Aug 10. [Article]

Step 14

Madan A, Graham RA, Carroll KM, Mudra DR, Burton LA, Krueger LA, Downey AD, Czerwinski M, Forster J, Ribadeneira MD, Gan LS, LeCluyse EL, Zech K, Robertson P Jr, Koch P, Antonian L, Wagner G, Yu L, Parkinson A: Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes. Drug Metab Dispos. 2003 Apr;31(4):421-31. doi: 10.1124/dmd.31.4.421. [Article] Zand R, Nelson SD, Slattery JT, Thummel KE, Kalhorn TF, Adams SP, Wright JM: Inhibition and induction of cytochrome P4502E1-catalyzed oxidation by isoniazid in humans. Clin Pharmacol Ther. 1993 Aug;54(2):142-9. [Article] Caro AA, Cederbaum AI: Inhibition of CYP2E1 catalytic activity in vitro by S-adenosyl-L-methionine. Biochem Pharmacol. 2005 Apr 1;69(7):1081-93. [Article] Spracklin DK, Emery ME, Thummel KE, Kharasch ED: Concordance between trifluoroacetic acid and hepatic protein trifluoroacetylation after disulfiram inhibition of halothane metabolism in rats. Acta Anaesthesiol Scand. 2003 Jul;47(6):765-70. [Article] Leclercq I, Desager JP, Horsmans Y: Inhibition of chlorzoxazone metabolism, a clinical probe for CYP2E1, by a single ingestion of watercress. Clin Pharmacol Ther. 1998 Aug;64(2):144-9. doi: 10.1016/S0009-9236(98)90147-3. [Article] Wang P, Pradhan K, Zhong XB, Ma X: Isoniazid metabolism and hepatotoxicity. Acta Pharm Sin B. 2016 Sep;6(5):384-392. doi: 10.1016/j.apsb.2016.07.014. Epub 2016 Aug 3. [Article] Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L57). Canadian Pharmacists Association. [ISBN:1-894402-22-7]

Step 15

Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [Article] Desta Z, Soukhova NV, Flockhart DA: Inhibition of cytochrome P450 (CYP450) isoforms by isoniazid: potent inhibition of CYP2C19 and CYP3A. Antimicrob Agents Chemother. 2001 Feb;45(2):382-92. doi: 10.1128/AAC.45.2.382-392.2001. [Article] Wen X, Wang JS, Neuvonen PJ, Backman JT: Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes. Eur J Clin Pharmacol. 2002 Jan;57(11):799-804. [Article] Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L56). Canadian Pharmacists Association. [ISBN:1-894402-22-7]

Step 16

Nishimura Y, Kurata N, Sakurai E, Yasuhara H: Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities. J Pharmacol Sci. 2004 Nov;96(3):293-300. Epub 2004 Nov 5. [Article] Clin-info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L56). Canadian Pharmacists Association. [ISBN:1-894402-22-7] Flockhart Table of Drug Interactions [Link]

Step 17

Desta Z, Soukhova NV, Flockhart DA: Inhibition of cytochrome P450 (CYP450) isoforms by isoniazid: potent inhibition of CYP2C19 and CYP3A. Antimicrob Agents Chemother. 2001 Feb;45(2):382-92. doi: 10.1128/AAC.45.2.382-392.2001. [Article]

Step 18

Nishimura Y, Kurata N, Sakurai E, Yasuhara H: Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities. J Pharmacol Sci. 2004 Nov;96(3):293-300. Epub 2004 Nov 5. [Article] Desta Z, Soukhova NV, Flockhart DA: Inhibition of cytochrome P450 (CYP450) isoforms by isoniazid: potent inhibition of CYP2C19 and CYP3A. Antimicrob Agents Chemother. 2001 Feb;45(2):382-92. doi: 10.1128/AAC.45.2.382-392.2001. [Article] Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L56). Canadian Pharmacists Association. [ISBN:1-894402-22-7]

Step 19

Zhou S, Yung Chan S, Cher Goh B, Chan E, Duan W, Huang M, McLeod HL: Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet. 2005;44(3):279-304. doi: 10.2165/00003088-200544030-00005. [Article]

Step 20

Meng X, Maggs JL, Usui T, Whitaker P, French NS, Naisbitt DJ, Park BK: Auto-oxidation of Isoniazid Leads to Isonicotinic-Lysine Adducts on Human Serum Albumin. Chem Res Toxicol. 2015 Jan 20;28(1):51-8. doi: 10.1021/tx500285k. Epub 2014 Dec 9. [Article]