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Clinical Pharmacokinetics of Metronidazole

Summary

The clinical pharmacokinetics of metronidazole following oral, intravenous, rectal, and intravaginal doses are described. Peak serum concentrations are quite similar after oral or intravenous administration and average approximately 10 μg/ml after a single 500mg dose. After an oral dose the peak serum concentration is reached approximately 1 hour after administration. Food does not significantly affect absorption, and the bioavailability of the dose approaches 100%. For both intravenous and oral administration, a linear dose-concentration curve pertained for usual therapeutic doses between 200 and 2000mg.

Multiple oral or intravenous doses given every 6 to 8 hours result in some drug accumulation with higher serum concentrations as compared with single doses. On an intravenous dose regimen of 500mg every 8 hours, maximum metronidazole serum concentrations average 25 μg/ml and minimum concentrations 15 μg/ml. Rectal administration of metronidazole by suppository resulted in peak serum concentrations approximately one-half those following equivalent oral doses and occurred at 4 hours after administration; the bioavailability of the rectal suppository was approximately 80%. From the limited data available, the systemic absorption of intravaginal metronidazole is very slow with peak serum concentrations of approximately 2 μg/ml being attained 8 to 24 hours after administration of a 500mg dose.

Metronidazole is excreted in the urine as unchanged drug and primarily oxidative metabolites, the major compounds being the hydroxy and acid metabolites. The degree of urinary excretion is dependent upon the assay used. By bioassay, 15 to 20% of the administered dose is excreted as bioactive drug. By high pressure liquid chromatography, in which unchanged metronidazole and the hydroxy and acid metabolites are measured separately, total excretion of these compounds after 48 hours is approximately 30%, with the hydroxy metabolite being the primary excretory product.

Detailed pharmacokinetic analysis of metronidazole has been performed using 1-compartment and 2-compartment open models. The serum half-life of unchanged metronidazole averaged 8.2 hours, as determined by specific chemical methods, whereas using bioassay methods the half-life was somewhat longer. A 2-compartment open model analysis described the serum concentration-time curve with a rapid a (distribution) phase (half-life 1.24 hours) and a slower β (elimination) phase (half-life 9.76 hours). Metronidazole has a large apparent volume of distribution and serum protein binding of 20% or less. In multiple-dose regimens the hydroxy metabolite of metronidazole may be present in concentrations up to 30% of those of the parent drug with a half-life of 9.7 hours. The acid metabolite is rarely detected in serum. Metronidazole is widely distributed throughout the body with tissue levels, in most cases, approximating serum levels. This is especially important in the central nervous system where the drug readily crosses both the blood-brain and blood-cerebrospinal fluid barriers.

The pharmacokinetics of metronidazole do not appear to differ significantly in neonates, patients seriously ill with anaerobic infections, or during pregnancy. However, dose modification is necessary in neonates because of the slower elimination of the drug. In patients with renal failure, although the serum half-life of metronidazole does not change, the half-life of the hydroxy metabolite increases 4-fold and accumulates in the serum. Haemodialysis effectively removes metronidazole and, to a lesser extent, the hydroxy metabolite, reducing the half-life of the former to 2.6 hours and the latter to 7.8 hours, and diarrhoea, a reversible leucocytopenia, and various neurological toxicities (the latter generally associated with large doses over a prolonged period). Potentially serious toxicities including tumourigenicity, dysmorphogenicity, and mutagenicity inferred from certain animal models and bacterial test systems have not been confirmed in humans.

The pharmacokinetic properties of metronidazole complement its excellent microbiological activity against anaerobic organisms, making it a very effective drug in the treatment of anaerobic infections.

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References

  1. Amon, I.; Amon, K. and Huller, H.: Pharmacokinetics and therapeutic efficacy of metronidazole at different dosages. International Journal of Clinical Pharmacology and Biopharmacy 16: 384–386 (1978).

    PubMed  CAS  Google Scholar 

  2. Amon, I.; Amon, K.; Franke, G. and Mohr, C.: Pharmacokinetics of metronidazole in pregnant women. Chemotherapy 27: 73–79 (1981).

    PubMed  Article  CAS  Google Scholar 

  3. Amon, I.; Kraatz. G.; Amon, K. and Peters, R.: Metronidazole in patients with renal insufficiency. Drugs Under Experimental and Clinical Research 8: 231–234 (1982).

    Google Scholar 

  4. Beard, C.N.; Noller, KL; Os’Fallon, W.P.N.; Kurland, L.T. and Dockerty, M.B.: Lack of evidence for cancer due to use of metronidazole. New England Journal of Medicine 301: 519–521 (1979).

    PubMed  Article  CAS  Google Scholar 

  5. Bergan, T. and Arnold, E.: Pharmacokinetics of metronidazole in healthy adult volunteers after tablets and suppositories. Chemotherapy 26: 231–241 (1980)

    PubMed  Article  CAS  Google Scholar 

  6. Bergan, T.; Bjerke, P.E.M. and Fausa, O.: Pharmacokinetics of metronidazole in patients with enteric disease compared to normal volunteers. Chemotherapy 27: 233–238 (1981).

    PubMed  Article  CAS  Google Scholar 

  7. Berman, B.W.; King Jr, F.H.; Rubenstein, D.S. and Long, S.S.: Bacleroides fragilis meningitis in a neonate successfully treated with metronidazole. Journal of Pediatrics 93: 793–795 (1978).

    PubMed  Article  CAS  Google Scholar 

  8. Bolton, R.P.: Oral metronidazole in Clostridium difficile positive antibiotic-associated diarrhea. Gut 21: A921 (1980).

    Google Scholar 

  9. Bryan, C.S.; Huffman, L.J.; Del Bene, V.E.; Sanders, C.V. and Scalcini, M.C.: Intravenous metronidazole therapy for Bacteroides fragilis meningitis. Southern Medical Journal 72: 494–497 (1979).

    PubMed  Article  CAS  Google Scholar 

  10. Busch. D.F.; Sutter, V.L. and Finegold, S.M.: Activity of combinations of antimicrobial agents against Bacleroides fragilis. Journal of Infectious Diseases 133: 321–328 (1976).

    PubMed  Article  CAS  Google Scholar 

  11. Cerat, G.A.; Cerat, L.L.; McHenry, M.C.; Wagner, J.G.; Hall, P.M. and Gavan, T.L.: Metronidazole in renal failure; in Finegold (Ed.) Metronidazole. Proceedings of the International Metronidazole Conference, Montreal, May, 1976, pp.404–414 (Excerpta Medica 1977).

    Google Scholar 

  12. Chow. A. W.; Bendnorz, D. and Guze, L.B.: Susceptibility of obligate anaerobes to metronidazole: an extended study of 1,054 clinical isolates; in Finegold (Ed.) Metronidazole. Proceedings of the International Metronidazole Conference, Montreal, May, 1976, pp.286–292 (Excerpta Medica 1977).

    Google Scholar 

  13. Coxon, A. and Pallis, C.A.; Metronidazole neuropathy. Journal of Neurology, Neurosurgery and Psychiatry 39; 403 (1976).

    Article  CAS  Google Scholar 

  14. Daneshmend, T.K.; Homeida, M.; Kaye, C.M.; Elamin, A.A. and Roberts, C.J.C.: Disposition of oral metronidazole in hepatic cirrhosis and in hepatosplenic schistosomiasis. Gut 23: 807–813 (1982).

    PubMed  Article  CAS  Google Scholar 

  15. DeSilva, J.A.F.; Munro, N. and Strojny, N.: Absorptiometric, polarographic, and gas chromatographic assays for the determinations of N-l-substituted nitroimidazoles in blood and urine. Journal of Pharmaceutical Sciences 59: 201–210 (1970).

    PubMed  Article  CAS  Google Scholar 

  16. Deutsch, G.; Foster, J.L.; McFadzean, J.A. and Parnell, A.: Human studies with high dose metronidazole: a non-toxic sensitizer of hypoxic cells. British Journal of Cancer 31: 75–80 (1975).

    PubMed  Article  CAS  Google Scholar 

  17. Douglas-Smith, B.J. and Wellingham, J.: Metronidazole in treatment of empyema. British Medical Journal 1: 1074–1076 (1976).

    Article  Google Scholar 

  18. Elder, M.G. and Kane, J.L.: The pelvic tissue levels achieved by metronidazole after single or multiple dosing — oral and rectal; in Phillips and Collier (Eds) Metronidazole. Proceedings of the Second International Symposium on Anaerobic Infections, Geneva, The Royal Society of Medicine, pp.55–58 (Academic Press, London/Grune and Stratton, New York 1979).

    Google Scholar 

  19. Erickson, S.H.; Oppenheim, G.L. and Smith, G.H.: Metronidazole in breast milk. Obstetrics and Gynecology 57: 48–50 (1981).

    PubMed  CAS  Google Scholar 

  20. Eykyn, S.J. and Phillips, I.: Metronidazole and anaerobic sepsis. British Medical Journal 2: 1418–1421 (1976).

    PubMed  Article  CAS  Google Scholar 

  21. Feldman, W.E.: Bacteroides fragilis ventriculitis and meningitis. Report of two cases. American Journal of Diseases of Children 130: 880–883 (1976).

    CAS  Google Scholar 

  22. Frytak. S.; Moertel, C.G.; Childs, D.S. and Albers, J.W.: Neurologic toxicity associated with high dose metronidazole therapy. Annals of Internal Medicine 88: 361–362 (1978).

    PubMed  CAS  Google Scholar 

  23. Gabriel. R.; Page, C.M.; Weller, I.V.D.; Collier, J.; Houghton, G.W.; Templeton, R. and Thorne, P.S.: The pharmacokinetics of metronidazole in patients with chronic renal failure; in Phillips and Collier (Eds) Metronidazole. Proceedings of the Second International Symposium on Anaerobic Infections, Geneva, April, 1979, The Royal Society of Medicine, pp.50–54 (Academic Press, London/Grune and Stratton, New York 1979).

    Google Scholar 

  24. George, R.H. and Bint, A.J.: Treatment of a brain abscess due to Bacteroides fragilis with metronidazole. Journal of Antimicrobial Chemotherapy 2: 101–102 (1977).

    Article  Google Scholar 

  25. George, W.L.; Sutter, V.L. and Finegold, S.M.: Toxigenicity and antimicrobial susceptibility of Clostridium difficile, a cause of antimicrobial agent-associated colitis. Current Microbiology 1: 55–58 (1978).

    Article  CAS  Google Scholar 

  26. Giamarellou, H.; Kanellakopoulou, K.; Pragastis, D.; Tagaris, N. and Daikos, G.K.: Treatment with metronidazole of 48 patients with serious anaerobic infections. Journal of Antimicrobial Chemotherapy 3: 347–353 (1977).

    PubMed  Article  CAS  Google Scholar 

  27. Gillin, F.D. and Diamond, L.S.: Inhibition of clonal growth of Giardia lamblia and Entamoeba histolytica by metronidazole, quinacrine, and other antimicrobial agents. Journal of Antimicrobial Chemotherapy 8: 305–316 (1981).

    PubMed  Article  CAS  Google Scholar 

  28. Gray, M.S.; Kane, P.O. and Squires, S.: Further observations on metronidazole (’Flagyl’). British Journal of Venereal Diseases 37: 278–279 (1961).

    PubMed  CAS  Google Scholar 

  29. Gulaid, A.; Houghton, G.W.; Lewellen, O.R.W.; Smith, J. and Thorne, P.S.: Determination of metronidazole and its two major metabolites in biological fluids by high pressure liquid chromatography. British Journal of Clinical Pharmacology 6: 430–432 (1978).

    PubMed  Article  CAS  Google Scholar 

  30. Holten, E. and Smith-Erichsen, N.: Concentration of metronidazole in serum during peritoneal dialysis. Chemotherapy 27: 414–415 (1981).

    PubMed  Article  CAS  Google Scholar 

  31. Houghton, G.W.; Smith, J.; Thorne, P.S. and Templeton, R.: The pharmacokinetics of oral and intravenous metronidazole in man. Journal of Antimicrobial Chemotherapy 5: 609–623 (1979a).

    Article  Google Scholar 

  32. Houghton, G.W.; Thorne, P.S.; Smith, J.; Templeton, R. and Collier, J.: Comparison of the pharmacokinetics of metronidazole in healthy female volunteers following either a single oral or intravenous dose. British Journal of Clinical Pharmacology 8: 337–341 (1979b).

    PubMed  Article  CAS  Google Scholar 

  33. Houghton, G.W.; Thorne, P.S.; Smith, J.; Templeton, R.; Collier, J.; Moesgaard, F. and Lykkegaard-Nielsen, M.: The pharmacokinetics of intravenous metronidazole (single and multiple dosing); in Phillips and Collier (Eds) Metronidazole. Proceedings of the Second International Symposium on Anaerobic Infections, Geneva, April, 1979, pp.35–40 (Academic Press, London/Grune and Stratton, New York 1979c).

    Google Scholar 

  34. Houghton, G.W.; Thorne, P.S.; Smith, J.; Templeton, R.; Cook, P.J. and James, I.M.: Plasma metronidazole concentrations after suppository administration; in Phillips and Collier (Eds) Metronidazole. Proceedings of the Second International Symposium on Anaerobic Infections, Geneva, April, 1979, pp.41–44 (Academic Press, London/Grune and Stratton, New York 1979d).

    Google Scholar 

  35. Ingham, H.R.; Rich, G.E.; Selkon, J.B.; Hale, J.H.; Roxby, C.M.; Betty, M.J.; Johnson, R.W.C. and Uldall, P.R.: Treatment with metronidazole of three patients with serious infections due to Bacteroides fragilis. Journal of Antimicrobial Chemotherapy 1: 235–242 (1975).

    PubMed  Article  CAS  Google Scholar 

  36. Ingham, H.R.; Selkon, J.B. and Roxby, C.M.: The bacteriology and chemotherapy of otogenic cerebral abscesses. Journal of Antimicrobial Chemotherapy 4 (Suppl. C): 63–69 (1978).

    PubMed  Article  Google Scholar 

  37. loannides, L.; Somogyi, A.; Spicer, J.; Heinzow, B.; Tong, N.; Franklin, C. and McLean, A.: Rectal administration of metronidazole provides therapeutic plasma levels in postoperative patients. New Eng. J. Med. 305: 1569–1570 (1981).

    Article  Google Scholar 

  38. Jager-Roman, E.; Doyle, P.E.; Baird-Lambert, J.; Cvejic, M. and Buchanan, N.: Pharmacokinetics and tissue distribution of metronidazole in the newborn infant. Journal of Pediatrics 100: 651–654 (1982).

    PubMed  Article  CAS  Google Scholar 

  39. Jennison, R.F.; Stenton, P. and Watt, L.: Laboratory studies with the systemic trichomonaside, metronidazole. Journal of Clinical Pathology 14: 431–435 (1961).

    PubMed  Article  CAS  Google Scholar 

  40. Jokipii, L.; Karma, P. and Jokipii, A.M.M.: Access of metronidazole into the chronically inflamed middle ear with reference to anaerobic bacterial infections. Archives of Oto-Rhino-Laryngology 220: 167–174 (1978).

    PubMed  Article  CAS  Google Scholar 

  41. Jokipii, A.M.M.; Myllyla, V.V.; Hokkanen, E. and Jokipii, L.: Penetration of blood brain barrier by metronidazole and tinidazole. Journal of Antimicrobial Chemotherapy 3: 239–245 (1977).

    PubMed  Article  CAS  Google Scholar 

  42. Kane, P.O.: Polarographic methods for the determinations of two anti-protozoal nitroimidazole derivatives in materials of biological and non-biological origin. Journal of the Polarographic Society 7: 58–62 (1961).

    Google Scholar 

  43. Kane, P.O.; McFadzean, J.A.; Squires, S.; King, A.J. and Nicol, C.S.: Absorption and excretion of metronidazole. Part 1. Serum concentration and urinary excretion after oral administration. British Journal of Venereal Disease 37: 273–275 (1961).

    CAS  Google Scholar 

  44. Kazmier, F.J.: A significant interaction between metronidazole and warfarin. Mayo Clinic Proceedings 51: 782–784 (1976).

    PubMed  CAS  Google Scholar 

  45. Khan, O. and Nixon, H.H.: The management of neonatal necrotizing enterocolitis 1977. A preliminary report. Zeitschrift fur Kinderchirurgie 25: 196–205 (1978).

    Google Scholar 

  46. Klotz, U.: Pathophysiological and disease-induced changes in drug distribution volume. Pharmacokinetic implications. Clinical Pharmacokinetics 1: 204–208 (1976).

    PubMed  Article  CAS  Google Scholar 

  47. Koch, R.L.; Beaulieau Jr, B.B.; Chrystal, E.J.T. and Goldman, P.: A metronidazole metabolite in human urine and its risk. Science 211: 398–400 (1981).

    Article  CAS  Google Scholar 

  48. Lane, I.F.; Pulvertaft, R.W. and Hewitt, W.G.: Serum metronidazole levels following rectal administration. Journal of Antimicrobial Chemotherapy 8: 425 (1981).

    Article  Google Scholar 

  49. Lau, E.P.K.; Yao, C.; Lewis, M. and Senkowski, B.Z.: Calorometric determination of some N-l-substituted nitroimidazoles. Journal of Pharmaceutical Sciences 58: 55–57 (1969).

    PubMed  Article  CAS  Google Scholar 

  50. Laufer, J.; Mignon, H. and Videau, D.: Ls’association métronidazole-spiramycine. Concentrations et synergie in situ comparées aux CMI de la flore buccale. Revue de Stomatologie et Chirurgie Maxillofaciale 74: 387–392 (1973).

    Google Scholar 

  51. Levison, M.E.: Microbiological agar diffusion assay for metronidazole concentrations in serum. Antimicrobial Agents and Chemotherapy 5: 466–468 (1974).

    PubMed  Article  CAS  Google Scholar 

  52. Lykkegaard-Nielsen, N. and Justesen, T.: Excretion of metronidazole in human bile. Investigations of hepatic bile, common duct bile and gall bladder bile. Scandinavian Journal of Gastroenterology 12: 1002–1008 (1977).

    Google Scholar 

  53. McGilveray, I.J.; Midha, K.K.; Loo, J.C.K. and Cooper, J.K.: The bioavailability of commercial metronidazole formulations. International Journal of Clinical Pharmacology 16: 110–115 (1978).

    CAS  Google Scholar 

  54. Melander, A.; Kahlmeter, G.; Kamme, C. and Ursing, B.: Bioavailability of metronidazole in fasting and non-fasting healthy subjects and in patients with Crohns’s disease. European Journal of Clinical Pharmacology 12: 69–72 (1977).

    PubMed  Article  CAS  Google Scholar 

  55. Midha, K.K.; McGilveray, I.J. and Cooper, J.K.: Determination of therapeutic levels of metronidazole in plasma by gas-liquid chromatography. Journal of Chromatography 87: 491–497 (1973).

    PubMed  Article  CAS  Google Scholar 

  56. Nastro, L.J. and Finegold, S.M.: Bactericidal activity of five antimicrobial agents against Bacteroides fragilis. Journal of Infectious Diseases 126: 104–107 (1972).

    PubMed  Article  CAS  Google Scholar 

  57. Nilsson-Ehle, I.; Ursing, B. and Nilsson-Ehle, P.: Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects. Antimicrobial Agents and Chemotherapy 19: 754–760 (1981).

    PubMed  Article  CAS  Google Scholar 

  58. Os’Grady, L.R. and Ralph, E.D.: Anaerobic meningitis and bacteremia caused by Fusobaclerium species. American Journal of Diseases in Children 130: 871–873 (1976).

    Google Scholar 

  59. Olumide, F. and Adesola, A.O.: Metronidazole retention enema in the management of severe intestinal amoebiasis. Nigerian Medical Journal 6: 2–8 (1976).

    PubMed  CAS  Google Scholar 

  60. Opperman, J.; Azamoff, D.; Hunt, W.; Shierk, D.; Muir, R. and Ranney, R.: Pharmacokinetics of intravenously administered 14C-metronidazole hydrochloride in man. Abstract of the Annual Meeting of the American Society of Microbiology, p.326 (1978a).

  61. Opperman, J.A.; Hunt, W.L.; Shierk, D. and Arnold, J.D.: Comparative disposition of 14C-metronidazole after its oral and intravaginal administration to female subjects. 18th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract 60, Atlanta, Georgia (1978b).

  62. Os’Reilly, R.A.: The stereoselective interaction of warfarin and metronidazole in man. New England Journal of Medicine 295: 354–357 (1976).

    Article  Google Scholar 

  63. Pashby, N.L.; Bolton, R.P. and Sherriff, R.J.: Oral metronidazole in Clostridium difficile colitis. British Medical Journal 1: 1605–1606 (1979).

    PubMed  Article  CAS  Google Scholar 

  64. Rabin, H.R.; Urtasun, R.C.; Partington, J.; Koziol, D.; Sharon, M. and Walker, K.: High dose metronidazole: pharmacokinetics and bioavailability using an I.V. preparation and application of its use as a radiosensitizer. Current Treatment Reports 64: 1087–1095 (1980).

    CAS  Google Scholar 

  65. Ralph, E.D. and Amatnieks, Y.: Serum levels of metronidazole and the hydroxy metabolite in renal failure (unpublished data).

  66. Ralph, E.D. and Austin, T.W.: Systemic absorption of intravaginal metronidazole. Paper presented at the Annual Meeting of the Royal College of Physicians and Surgeons, Toronto, September 1981.

    Google Scholar 

  67. Ralph, E.D. and Clark, D.A.: Inactivation of metronidazole by anaerobic and aerobic bacteria. Antimicrobial Agents and Chemotherapy 14: 377–383 (1978).

    PubMed  Article  CAS  Google Scholar 

  68. Ralph, E.D.; Clarke, J.T.; Libke, R.D.; Luthy, R.P. and Kirby.: Pharmacokinetics of metronidazole as determined by bioassay. Antimicrobial Agents and Chemotherapy 6: 691–696 (1974).

    PubMed  Article  CAS  Google Scholar 

  69. Ralph, E.D. and Kirby, W.M.M.: Bioassay of metronidazole with either anaerobic or aerobic incubation. Journal of Infectious Diseases 132: 587–591 (1975).

    PubMed  Article  CAS  Google Scholar 

  70. Ramsay, I.D.: Endocrine ophthalmolopathy. British Medical Journal 4: 706 (1968).

    PubMed  Article  CAS  Google Scholar 

  71. Roe, F.J.C.: Metronidazole: review of uses and toxicity. Journal of Antimicrobial Chemotherapy 3: 205–212 (1977).

    PubMed  Article  CAS  Google Scholar 

  72. Rood, J.P. and Collier, J.: Metronidazole in alveolar bone; in Phillips and Collier (Eds) Metronidazole. Proceedings of the Second International Symposium on Anaerobic Infections, Geneva, April, 1979, The Royal Society of Medicine, pp.45–47 (Academic Press, London/Grune and Stratton, New York 1979).

    Google Scholar 

  73. Sanvordeker, D.R.; Chien, Y.W.; Lin, T.K. and Lambert, H.J.: Binding of metronidazole and its derivatives to plasma proteins: an assessment of drug binding phenomenon. Journal of Pharmaceutical Sciences 64: 1797–1803 (1975).

    PubMed  Article  CAS  Google Scholar 

  74. Schram, M. and Kleinman, H.: Use of metronidazole in the treatment of trichomoniasis. American Journal of Obstetrics and Gynaecology 83: 1284–1287 (1962).

    CAS  Google Scholar 

  75. Schwartz, D.E. and Jeunet, F.: Comparative pharmacokinetic studies of ornidazole and metronidazole in man. Chemotherapy (Basel) 22: 19–29 (1976).

    CAS  Google Scholar 

  76. Searle, A.J.F. and Willson, R.L.: Metronidazole (Flagyl): Degradation by the intestinal flora. Xenobiotica 6: 457–464 (1976).

    PubMed  Article  CAS  Google Scholar 

  77. Semer. J.M.; Friedland, P.; Vaisberg, M. and Greenberg, M.: The use of metronidazole in the treatment of alcoholism. American Journal of Psychiatry 123: 722–724 (1966).

    PubMed  CAS  Google Scholar 

  78. Smith, J.A.: Neutropenia associated with metronidazole therapy. Canadian Medical Association Journal 123: 202 (1980).

    PubMed  CAS  Google Scholar 

  79. Stambaugh. J.E.; Feo, L.G. and Manthei, R.W.: The isolation and identification of the urinary oxidative metabolites of metronidazole in man. Journal of Pharmacology and Experimental Therapeutics 161: 373–381 (1968).

    PubMed  CAS  Google Scholar 

  80. Study Group: An evaluation of metronidazole in the prophylaxis and treatment of anaerobic infections in surgical patients. Journal of Antimicrobial Chemotherapy 1: 393–401 (1975).

    Article  Google Scholar 

  81. Study Group: An evaluation of metronidazole in the prophylaxis of anaerobic infections in obstetrical patients. Journal of Antimicrobial Chemotherapy 4 (Suppl. C): 55–62 (1978).

    Article  Google Scholar 

  82. Sutter, V.L. and Finegold, S.M.: Susceptibility of anaerobic bacteria to 23 antimicrobial agents. Antimicrobial Agents and Chemotherapy 10: 736–752 (1976).

    PubMed  Article  CAS  Google Scholar 

  83. Taylor Jr. J.A.; Migliardi, J.R. and Von Wittenau, M.S.: Tini-dazole and metronidazole pharmacokinetics in man and mouse. Antimicrobial Agents and Chemotherapy: 267-270 (1969).

  84. Thomson, G.; Clark, A.H.; Hare, K. and Spilg, W.G.: Pseudomembranous colitis after treatment with metronidazole. British Medical Journal 282: 864–865 (1981).

    PubMed  Article  CAS  Google Scholar 

  85. Urtasun, R.C.; Band, P.; Rabin, H. and Chapman, J.D.: The use of high dose metronidazole in clinical oncology; in Finegold (Ed.) Metronidazole. Proceedings of the International Metronidazole Conference, Montreal, May, 1976, pp. 185–192 (Excerpta Medica, 1977).

    Google Scholar 

  86. Urtasun, R.C.; Sturmwind, J.; Rabin, H.; Band, P.R. and Chapman, J.D.: ‘High-dose’ metronidazole: a preliminary pharmacological study prior to its investigational use in clinical radiotherapy trials. British Journal of Radiology 47: 297–299 (1974).

    PubMed  Article  CAS  Google Scholar 

  87. Warner, J.F.; Perkins, R.L. and Cordero, L.: Metronidazole therapy of anaerobic bacteremia, meningitis and brain abscess. Archives of Internal Medicine 139: 167–169 (1979).

    PubMed  Article  CAS  Google Scholar 

  88. Welling, P.G. and Monro, A.M.: The pharmacokinetics of metronidazole and tinidazole in man. Arzneimittel-Forschung 22: 2128–2132 (1972).

    PubMed  CAS  Google Scholar 

  89. Wheeler, L.A.; DeMeo, M.; Halula, M.; George, L. and Heseltine, P.: Use of high pressure liquid chromatography to determine plasma levels of metronidazole and metabolites after intravenous administration. Antimicrobial Agents and Chemotherapy 13: 205–209 (1978).

    PubMed  Article  CAS  Google Scholar 

  90. Wood, B.A. and Monro, A.M.: Pharmacokinetics of tinidazole and metronidazole in women after single large oral doses. British Journal of Venereal Diseases 48: 51–53 (1975).

    Google Scholar 

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Ralph, E.D. Clinical Pharmacokinetics of Metronidazole. Clin Pharmacokinet 8, 43–62 (1983). https://doi.org/10.2165/00003088-198308010-00003

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Keywords

  • Metronidazole
  • Clinical Pharmacokinetic
  • Acid Metabolite
  • Peak Serum Concentration
  • Anaerobic Infection