8/14/2020 Metronidazole: An overview - UpToDate

Author: Melissa Johnson, PharmD

Section Editor: David C Hooper, MD
Deputy Editor: Sheila Bond, MD

INTRODUCTION

Metronidazole is one of the mainstay drugs for the treatment of anaerobic infections [1,2]. It is
approved by the US Food and Drug Administration for the treatment of anaerobic and protozoal
infections. Metronidazole exerts its antimicrobial effects through the production of free radicals
that are toxic to the microbe.

The use of metronidazole for treating specific infections is discussed separately. (See "Anaerobic
bacterial infections" and "Clostridioides (formerly Clostridium) difficile infection in adults:
Treatment and prevention" and "Intestinal Entamoeba histolytica amebiasis" and "Extraintestinal
Entamoeba histolytica amebiasis" and "Trichomoniasis".)

MECHANISM OF ACTION

Activity against most obligate anaerobes occurs through a four-step process:

● Entry into the microorganism – Metronidazole is a low molecular weight compound that
diffuses across the cell membranes of anaerobic and aerobic microorganisms. However,
antimicrobial activity is limited to anaerobes [3].
● Reductive activation by intracellular transport proteins – Metronidazole is reduced by the
pyruvate:ferredoxin oxidoreductase system in obligate anaerobes, which alters its chemical
structure. Pyruvate:ferredoxin oxidoreductase normally generates adenosine triphosphate
(ATP) via oxidative decarboxylation of pyruvate. With metronidazole in the cellular
environment, its nitro group acts as an electron sink, capturing electrons that would usually
be transferred to hydrogen ions in this cycle. Reduction of metronidazole creates a
concentration gradient that drives uptake of more drug and promotes formation of
intermediate compounds and free radicals that are toxic to the cell [3-5].

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Literature review current through: Jul 2020. | This topic last updated: Sep 05, 2019.

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REFERENCES

1. Löfmark S, Edlund C, Nord CE. Metronidazole is still the drug of choice for treatment of
anaerobic infections. Clin Infect Dis 2010; 50 Suppl 1:S16.

2. Dingsdag SA, Hunter N. Metronidazole: an update on metabolism, structure-cytotoxicity

and resistance mechanisms. J Antimicrob Chemother 2018; 73:265.

3. Edwards DI. Nitroimidazole drugs--action and resistance mechanisms. I. Mechanisms of

action. J Antimicrob Chemother 1993; 31:9.

4. Edwards DI. Reduction of nitroimidazoles in vitro and DNA damage. Biochem Pharmacol
1986; 35:53.

5. Müller M. Reductive activation of nitroimidazoles in anaerobic microorganisms. Biochem

Pharmacol 1986; 35:37.

6. Tocher JH, Edwards DI. The interaction of reduced metronidazole with DNA bases and
nucleosides. Int J Radiat Oncol Biol Phys 1992; 22:661.

7. Tocher JH, Edwards DI. Evidence for the direct interaction of reduced metronidazole
derivatives with DNA bases. Biochem Pharmacol 1994; 48:1089.

8. Goldman P, Koch RL, Yeung TC, et al. Comparing the reduction of nitroimidazoles in
bacteria and mammalian tissues and relating it to biological activity. Biochem Pharmacol
1986; 35:43.

9. Stratton CW, Weeks LS, Aldridge KE. Comparison of the bactericidal activity of
clindamycin and metronidazole against cefoxitin-susceptible and cefoxitin-resistant isolates
of the Bacteroides fragilis group. Diagn Microbiol Infect Dis 1991; 14:377.

https://www.uptodate.com/contents/metronidazole-an-overview 2/11
8/14/2020 Metronidazole: An overview - UpToDate

10. Stratton CW, Weeks LS, Aldridge KE. Inhibitory and bactericidal activity of selected beta-
lactam agents alone and in combination with beta-lactamase inhibitors compared with that
of cefoxitin and metronidazole against cefoxitin-susceptible and cefoxitin-resistant isolates
of the Bacteroides fragilis group. Diagn Microbiol Infect Dis 1992; 15:321.

11. Ravdin JI, Skilogiannis J. In vitro susceptibilities of Entamoeba histolytica to azithromycin,

CP-63,956, erythromycin, and metronidazole. Antimicrob Agents Chemother 1989; 33:960.

12. Nix DE, Tyrrell R, Müller M. Pharmacodynamics of metronidazole determined by a time-kill

assay for Trichomonas vaginalis. Antimicrob Agents Chemother 1995; 39:1848.

13. Ralph ED, Kirby WM. Unique bactericidal action of metronidazole against Bacteroides
fragilis and Clostridium perfringens. Antimicrob Agents Chemother 1975; 8:409.

14. Ralph ED, Amatnieks YE. Potentially synergistic antimicrobial combinations with
metronidazole against Bacteroides fragilis. Antimicrob Agents Chemother 1980; 17:379.

15. Cuchural GJ Jr, Tally FP, Jacobus NV, et al. Antimicrobial susceptibilities of 1,292 isolates
of the Bacteroides fragilis group in the United States: comparison of 1981 with 1982.
Antimicrob Agents Chemother 1984; 26:145.

16. Musial CE, Rosenblatt JE. Antimicrobial susceptibilities of anaerobic bacteria isolated at
the Mayo Clinic during 1982 through 1987: comparison with results from 1977 through
1981. Mayo Clin Proc 1989; 64:392.

17. Snydman DR, Jacobus NV, McDermott LA, et al. Multicenter study of in vitro susceptibility
of the Bacteroides fragilis group, 1995 to 1996, with comparison of resistance trends from
1990 to 1996. Antimicrob Agents Chemother 1999; 43:2417.

18. Aldridge KE, Ashcraft D, O'Brien M, Sanders CV. Bacteremia due to Bacteroides fragilis
group: distribution of species, beta-lactamase production, and antimicrobial susceptibility
patterns. Antimicrob Agents Chemother 2003; 47:148.

19. Snydman DR, Jacobus NV, McDermott LA, et al. Lessons learned from the anaerobe
survey: historical perspective and review of the most recent data (2005-2007). Clin Infect
Dis 2010; 50 Suppl 1:S26.

20. Centers for Disease Control and Prevention (CDC). Multidrug-resistant bacteroides fragilis-
-Seattle, Washington, 2013. MMWR Morb Mortal Wkly Rep 2013; 62:694.

21. Merchan C, Parajuli S, Siegfried J, et al. Multidrug-Resistant Bacteroides fragilis

Bacteremia in a US Resident: An Emerging Challenge. Case Rep Infect Dis 2016;
2016:3607125.

https://www.uptodate.com/contents/metronidazole-an-overview 3/11
8/14/2020 Metronidazole: An overview - UpToDate

22. Sherwood JE, Fraser S, Citron DM, et al. Multi-drug resistant Bacteroides fragilis
recovered from blood and severe leg wounds caused by an improvised explosive device
(IED) in Afghanistan. Anaerobe 2011; 17:152.

23. Sethi S, Shukla R, Bala K, et al. Emerging metronidazole resistance in Bacteroides spp.
and its association with the nim gene: a study from North India. J Glob Antimicrob Resist
2019; 16:210.

24. Brazier JS, Stubbs SL, Duerden BI. Metronidazole resistance among clinical isolates
belonging to the Bacteroides fragilis group: time to be concerned? J Antimicrob Chemother
1999; 44:580.

25. Barbut F, Decré D, Burghoffer B, et al. Antimicrobial susceptibilities and serogroups of

clinical strains of Clostridium difficile isolated in France in 1991 and 1997. Antimicrob
Agents Chemother 1999; 43:2607.

26. Reysset G, Haggoud A, Sebald M. Genetics of resistance of Bacteroides species to 5-

nitroimidazole. Clin Infect Dis 1993; 16 Suppl 4:S401.

27. Rasmussen BA, Bush K, Tally FP. Antimicrobial resistance in Bacteroides. Clin Infect Dis
1993; 16 Suppl 4:S390.

28. Narikawa S, Suzuki T, Yamamoto M, Nakamura M. Lactate dehydrogenase activity as a

cause of metronidazole resistance in Bacteroides fragilis NCTC 11295. J Antimicrob
Chemother 1991; 28:47.

29. Results of a multicentre European survey in 1991 of metronidazole resistance in

Helicobacter pylori. European Study Group on Antibiotic Susceptibility of Helicobacter
pylori. Eur J Clin Microbiol Infect Dis 1992; 11:777.

30. Adamek RJ, Suerbaum S, Pfaffenbach B, Opferkuch W. Primary and acquired

Helicobacter pylori resistance to clarithromycin, metronidazole, and amoxicillin--influence
on treatment outcome. Am J Gastroenterol 1998; 93:386.

31. Mégraud F, Lehn N, Lind T, et al. Antimicrobial susceptibility testing of Helicobacter pylori in
a large multicenter trial: the MACH 2 study. Antimicrob Agents Chemother 1999; 43:2747.

32. Lacey SL, Moss SF, Taylor GW. Metronidazole uptake by sensitive and resistant isolates of
Helicobacter pylori. J Antimicrob Chemother 1993; 32:393.

33. Moore RA, Beckthold B, Bryan LE. Metronidazole uptake in Helicobacter pylori. Can J
Microbiol 1995; 41:746.

https://www.uptodate.com/contents/metronidazole-an-overview 4/11
8/14/2020 Metronidazole: An overview - UpToDate

34. van Zwet AA, Thijs JC, Schievink-de Vries W, et al. In vitro studies on stability and
development of metronidazole resistance in Helicobacter pylori. Antimicrob Agents
Chemother 1994; 38:360.

35. Tankovic J, Lamarque D, Delchier JC, et al. Frequent association between alteration of the
rdxA gene and metronidazole resistance in French and North African isolates of
Helicobacter pylori. Antimicrob Agents Chemother 2000; 44:608.

36. Logan RP, Gummett PA, Misiewicz JJ, et al. One week eradication regimen for
Helicobacter pylori. Lancet 1991; 338:1249.

37. Owen RJ, Bell GD, Desai M, et al. Biotype and molecular fingerprints of metronidazole-
resistant strains of Helicobacter pylori from antral gastric mucosa. J Med Microbiol 1993;
38:6.

38. Wong WM, Gu Q, Wang WH, et al. Effects of primary metronidazole and clarithromycin
resistance to Helicobacter pylori on omeprazole, metronidazole, and clarithromycin triple-
therapy regimen in a region with high rates of metronidazole resistance. Clin Infect Dis
2003; 37:882.

39. Dore MP, Leandro G, Realdi G, et al. Effect of pretreatment antibiotic resistance to
metronidazole and clarithromycin on outcome of Helicobacter pylori therapy: a meta-
analytical approach. Dig Dis Sci 2000; 45:68.

40. Krajden S, Lossick JG, Wilk E, et al. Persistent Trichomonas vaginalis infection due to a
metronidazole-resistant strain. CMAJ 1986; 134:1373.

41. Müller M, Meingassner JG, Miller WA, Ledger WJ. Three metronidazole-resistant strains of
Trichomonas vaginalis from the United States. Am J Obstet Gynecol 1980; 138:808.

42. Dombrowski MP, Sokol RJ, Brown WJ, Bronsteen RA. Intravenous therapy of
metronidazole-resistant Trichomonas vaginalis. Obstet Gynecol 1987; 69:524.

43. Kulda J. Trichomonads, hydrogenosomes and drug resistance. Int J Parasitol 1999;
29:199.

44. Edwards DI. Nitroimidazole drugs--action and resistance mechanisms. II. Mechanisms of
resistance. J Antimicrob Chemother 1993; 31:201.

45. Quon DV, d'Oliveira CE, Johnson PJ. Reduced transcription of the ferredoxin gene in
metronidazole-resistant Trichomonas vaginalis. Proc Natl Acad Sci U S A 1992; 89:4402.

46. Nguyen MH, Yu VL, Morris AJ, et al. Antimicrobial resistance and clinical outcome of
Bacteroides bacteremia: findings of a multicenter prospective observational trial. Clin Infect

https://www.uptodate.com/contents/metronidazole-an-overview 5/11
8/14/2020 Metronidazole: An overview - UpToDate

Dis 2000; 30:870.

47. Baron EJ, Ropers G, Summanen P, Courcol RJ. Bactericidal activity of selected
antimicrobial agents against Bilophila wadsworthia and Bacteroides gracilis. Clin Infect Dis
1993; 16 Suppl 4:S339.

48. Pankuch GA, Jacobs MR, Appelbaum PC. Susceptibilities of 428 gram-positive and -
negative anaerobic bacteria to Bay y3118 compared with their susceptibilities to
ciprofloxacin, clindamycin, metronidazole, piperacillin, piperacillin-tazobactam, and
cefoxitin. Antimicrob Agents Chemother 1993; 37:1649.

49. Sheikh W, Pitkin DH, Nadler H. Antibacterial activity of meropenem and selected
comparative agents against anaerobic bacteria at seven North American centers. Clin
Infect Dis 1993; 16 Suppl 4:S361.

50. Alexander CJ, Citron DM, Brazier JS, Goldstein EJ. Identification and antimicrobial
resistance patterns of clinical isolates of Clostridium clostridioforme, Clostridium innocuum,
and Clostridium ramosum compared with those of clinical isolates of Clostridium
perfringens. J Clin Microbiol 1995; 33:3209.

51. Brazier JS, Levett PN, Stannard AJ, et al. Antibiotic susceptibility of clinical isolates of
clostridia. J Antimicrob Chemother 1985; 15:181.

52. Goldstein EJ, Citron DM, Cherubin CE, Hillier SL. Comparative susceptibility of the
Bacteroides fragilis group species and other anaerobic bacteria to meropenem, imipenem,
piperacillin, cefoxitin, ampicillin/sulbactam, clindamycin and metronidazole. J Antimicrob
Chemother 1993; 31:363.

53. Jones BM, Geary I, Lee ME, Duerden BI. Comparison of the in vitro activities of
fenticonazole, other imidazoles, metronidazole, and tetracycline against organisms
associated with bacterial vaginosis and skin infections. Antimicrob Agents Chemother
1989; 33:970.

54. Spiegel CA. Susceptibility of Mobiluncus species to 23 antimicrobial agents and 15 other
compounds. Antimicrob Agents Chemother 1987; 31:249.

55. Bannatyne RM, Jackowski J, Cheung R, Biers K. Susceptibility of Gardnerella vaginalis to

metronidazole, its bioactive metabolites, and tinidazole. Am J Clin Pathol 1987; 87:640.

56. Easmon CS, Ison CA, Kaye CM, et al. Pharmacokinetics of metronidazole and its principal
metabolites and their activity against Gardnerella vaginalis. Br J Vener Dis 1982; 58:246.

57. Lau AH, Lam NP, Piscitelli SC, et al. Clinical pharmacokinetics of metronidazole and other
nitroimidazole anti-infectives. Clin Pharmacokinet 1992; 23:328.

https://www.uptodate.com/contents/metronidazole-an-overview 6/11
8/14/2020 Metronidazole: An overview - UpToDate

58. Jokipii AM, Myllylä VV, Hokkanen E, Jokipii L. Penetration of the blood brain barrier by
metronidazole and tinidazole. J Antimicrob Chemother 1977; 3:239.

59. Warner JF, Perkins RL, Cordero L. Metronidazole therapy of anaerobic bacteremia,
meningitis, and brain abscess. Arch Intern Med 1979; 139:167.

60. Karjagin J, Pähkla R, Karki T, Starkopf J. Distribution of metronidazole in muscle tissue of

patients with septic shock and its efficacy against Bacteroides fragilis in vitro. J Antimicrob
Chemother 2005; 55:341.

61. Karjagin J, Pähkla R, Starkopf J. Perioperative penetration of metronidazole into muscle

tissue: a microdialysis study. Eur J Clin Pharmacol 2004; 59:809.

62. Nielsen ML, Justesen T. Excretion of metroindazole in human bile. Investigations of hepatic
bile, common duct bile, and gallbladder bile. Scand J Gastroenterol 1977; 12:1003.

63. Jensen JC, Gugler R. Single- and multiple-dose metronidazole kinetics. Clin Pharmacol
Ther 1983; 34:481.

64. Kreeft JH, Ogilvie RI, Dufresne LR. Metronidazole kinetics in dialysis patients. Surgery
1983; 93:149.

65. Lau AH, Chang CW, Sabatini S. Hemodialysis clearance of metronidazole and its
metabolites. Antimicrob Agents Chemother 1986; 29:235.

66. Roux AF, Moirot E, Delhotal B, et al. Metronidazole kinetics in patients with acute renal
failure on dialysis: a cumulative study. Clin Pharmacol Ther 1984; 36:363.

67. Somogyi A, Kong C, Sabto J, et al. Disposition and removal of metronidazole in patients
undergoing haemodialysis. Eur J Clin Pharmacol 1983; 25:683.

68. Guay DR, Meatherall RC, Baxter H, et al. Pharmacokinetics of metronidazole in patients
undergoing continuous ambulatory peritoneal dialysis. Antimicrob Agents Chemother 1984;
25:306.

69. Farrell G, Baird-Lambert J, Cvejic M, Buchanan N. Disposition and metabolism of

metronidazole in patients with liver failure. Hepatology 1984; 4:722.

70. Farrell G, Buchanan N, Baird-Lambert J. Impaired elimination of metronidazole in

decompensated chronic liver disease. Br Med J (Clin Res Ed) 1984; 288:1009.

71. Daneshmend TK, Roberts CJ. Impaired elimination of metronidazole in decompensated

chronic liver disease. Br Med J (Clin Res Ed) 1984; 288:405.

https://www.uptodate.com/contents/metronidazole-an-overview 7/11
8/14/2020 Metronidazole: An overview - UpToDate

72. Plaisance KI, Quintiliani R, Nightingale CH. The pharmacokinetics of metronidazole and its
metabolites in critically ill patients. J Antimicrob Chemother 1988; 21:195.

73. Lau AH, Evans R, Chang CW, Seligsohn R. Pharmacokinetics of metronidazole in patients
with alcoholic liver disease. Antimicrob Agents Chemother 1987; 31:1662.

74. Upadhyaya P, Bhatnagar V, Basu N. Pharmacokinetics of intravenous metronidazole in

neonates. J Pediatr Surg 1988; 23:263.

75. Kusumi RK, Plouffe JF, Wyatt RH, Fass RJ. Central nervous system toxicity associated
with metronidazole therapy. Ann Intern Med 1980; 93:59.

76. Lamp KC, Freeman CD, Klutman NE, Lacy MK. Pharmacokinetics and pharmacodynamics
of the nitroimidazole antimicrobials. Clin Pharmacokinet 1999; 36:353.

77. Urtasun RC, Rabin HR, Partington J. Human pharmacokinetics and toxicity of high-dose
metronidazole administered orally and intravenously. Surgery 1983; 93:145.

78. Saginur R, Hawley CR, Bartlett JG. Colitis associated with metronidazole therapy. J Infect
Dis 1980; 141:772.

79. Frytak S, Moertel CH, Childs DS. Neurologic toxicity associated with high-dose
metronidazole therapy. Ann Intern Med 1978; 88:361.

80. Halloran TJ. Convulsions associated with high cumulative doses of metronidazole. Drug
Intell Clin Pharm 1982; 16:409.

81. Farmakiotis D, Zeluff B. IMAGES IN CLINICAL MEDICINE. Metronidazole-Associated

Encephalopathy. N Engl J Med 2016; 374:1465.

82. Lefkowitz A, Shadowitz S. Reversible cerebellar neurotoxicity induced by metronidazole.

CMAJ 2018; 190:E961.

83. Kim E, Na DG, Kim EY, et al. MR imaging of metronidazole-induced encephalopathy:

lesion distribution and diffusion-weighted imaging findings. AJNR Am J Neuroradiol 2007;
28:1652.

84. Carroll MW, Jeon D, Mountz JM, et al. Efficacy and safety of metronidazole for pulmonary
multidrug-resistant tuberculosis. Antimicrob Agents Chemother 2013; 57:3903.

85. Knowles S, Choudhury T, Shear NH. Metronidazole hypersensitivity. Ann Pharmacother

1994; 28:325.

86. Cina SJ, Russell RA, Conradi SE. Sudden death due to metronidazole/ethanol interaction.
Am J Forensic Med Pathol 1996; 17:343.

https://www.uptodate.com/contents/metronidazole-an-overview 8/11
8/14/2020 Metronidazole: An overview - UpToDate

87. Williams CS, Woodcock KR. Do ethanol and metronidazole interact to produce a
disulfiram-like reaction? Ann Pharmacother 2000; 34:255.

88. Alexander I. 'Alcohol-antabuse' syndrome in patients receiving metronidazole during

gynaecological treatment. Br J Clin Pract 1985; 39:292.

89. Plosker GL. Possible interaction between ethanol and vaginally administered
metronidazole. Clin Pharm 1987; 6:189, 192.

90. Visapää JP, Tillonen JS, Kaihovaara PS, Salaspuro MP. Lack of disulfiram-like reaction
with metronidazole and ethanol. Ann Pharmacother 2002; 36:971.

91. Tillonen J, Väkeväinen S, Salaspuro V, et al. Metronidazole increases intracolonic but not
peripheral blood acetaldehyde in chronic ethanol-treated rats. Alcohol Clin Exp Res 2000;
24:570.

92. McKendrick MW, Geddes AM. Neutropenia associated with metronidazole. Br Med J 1979;
2:795.

93. Smith JA. Neutropenia associated with metronidazole therapy. Can Med Assoc J 1980;
123:202.

94. Celifarco A, Warschauer C, Burakoff R. Metronidazole-induced pancreatitis. Am J

Gastroenterol 1989; 84:958.

95. Sanford KA, Mayle JE, Dean HA, Greenbaum DS. Metronidazole-associated pancreatitis.
Ann Intern Med 1988; 109:756.

96. Altın C, Kanyılmaz S, Baysal S, Özin B. QT interval prolongation due to metronidazole

administration. Anadolu Kardiyol Derg 2011; 11:468.

97. Cohen O, Saar N, Swartzon M, et al. First report of metronidazole-induced QT interval

prolongation. Int J Antimicrob Agents 2008; 31:180.

98. Poluzzi E, Raschi E, Motola D, et al. Antimicrobials and the risk of torsades de pointes: the
contribution from data mining of the US FDA Adverse Event Reporting System. Drug Saf
2010; 33:303.

99. Powell SJ. The cardiotoxicity of systemic amebicides. A comparative electrocardiographic

study. Am J Trop Med Hyg 1967; 16:447.

100. Teicher MH, Altesman RI, Cole JO, Schatzberg AF. Possible nephrotoxic interaction of
lithium and metronidazole. JAMA 1987; 257:3365.

https://www.uptodate.com/contents/metronidazole-an-overview 9/11
8/14/2020 Metronidazole: An overview - UpToDate

101. Lassen E. Effects of acute and short-time antibiotic treatment on renal lithium elimination
and serum lithium levels in the rat. Acta Pharmacol Toxicol (Copenh) 1985; 56:273.

102. Blyden GT, Scavone JM, Greenblatt DJ. Metronidazole impairs clearance of phenytoin but
not of alprazolam or lorazepam. J Clin Pharmacol 1988; 28:240.

103. O'Reilly RA. The stereoselective interaction of warfarin and metronidazole in man. N Engl J
Med 1976; 295:354.

104. Patterson BD. Possible interaction between metronidazole and carbamazepine. Ann
Pharmacother 1994; 28:1303.

105. Kounas SP, Letsas KP, Sideris A, et al. QT interval prolongation and torsades de pointes
due to a coadministration of metronidazole and amiodarone. Pacing Clin Electrophysiol
2005; 28:472.

106. Panduranga P, Al-Mukhaini M, Rajarao MP. Multi-factorial causes of torsade de pointes in

a hospitalised surgical patient. Sultan Qaboos Univ Med J 2013; 13:152.

107. Zylber-Katz E, Rubinger D, Berlatzky Y. Cyclosporine interactions with metronidazole and

cimetidine. Drug Intell Clin Pharm 1988; 22:504.

108. Herzig K, Johnson DW. Marked elevation of blood cyclosporin and tacrolimus levels due to
concurrent metronidazole therapy. Nephrol Dial Transplant 1999; 14:521.

109. Page RL 2nd, Klem PM, Rogers C. Potential elevation of tacrolimus trough concentrations
with concomitant metronidazole therapy. Ann Pharmacother 2005; 39:1109.

110. Early CR, Park JM, Dorsch MP, et al. Effect of metronidazole use on tacrolimus
concentrations in transplant patients treated for Clostridium difficile. Transpl Infect Dis
2016; 18:714.

111. Nilsson C, Aschan J, Hentschke P, et al. The effect of metronidazole on busulfan

pharmacokinetics in patients undergoing hematopoietic stem cell transplantation. Bone
Marrow Transplant 2003; 31:429.

112. Eradiri O, Jamali F, Thomson AB. Interaction of metronidazole with phenobarbital,

cimetidine, prednisone, and sulfasalazine in Crohn's disease. Biopharm Drug Dispos 1988;
9:219.

113. Mead PB, Gibson M, Schentag JJ, Ziemniak JA. Possible alteration of metronidazole
metabolism by phenobarbital. N Engl J Med 1982; 306:1490.

114. Loft S, Døssing M, Sonne J, et al. Lack of effect of cimetidine on the pharmacokinetics and
metabolism of a single oral dose of metronidazole. Eur J Clin Pharmacol 1988; 35:65.
https://www.uptodate.com/contents/metronidazole-an-overview 10/11
8/14/2020 Metronidazole: An overview - UpToDate

115. Rajnarayana K, Reddy MS, Vidyasagar J, Krishna DR. Study on the influence of silymarin
pretreatment on metabolism and disposition of metronidazole. Arzneimittelforschung 2004;
54:109.

116. Loft S, Sonne J, Døssing M, Andreasen PB. Metronidazole pharmacokinetics in patients

with hepatic encephalopathy. Scand J Gastroenterol 1987; 22:117.

https://www.uptodate.com/contents/metronidazole-an-overview 11/11