Horatio B Fung1, Thien-Ly Doan. 1. Medical/Surgical Patient Care Center, James J. Peters Veterans Affairs Medical Center, Bronx, New York 10468, USA. horatio.fung@med.va.gov
Abstract
BACKGROUND: Tinidazole, a structural analogue of metrondazole, is an antiprotozoal agent that has been widely used in Europe and developing countries for >2 decades with established efficacy and acceptable tolerability. It was recently approved by the US Food and Drug Administration for the treatment of trichomoniasis, giardiasis, amebiasis, and amebic liver abscess. OBJECTIVE: This article reviews the pharmacologic and pharmacokinetic properties and clinical usefulness of tinidazole. METHODS: Relevant information was identified through a search of MEDLINE (1966-August 2005), Iowa Drug Information Service (1966-August 2005), and International Pharmaceutical Abstracts (1970-August 2005) using the terms tinidazole, Fasigyn, and nitroimidazole. RESULTS: In vitro, tinidazole exhibits activity against pathogenic protozoa (eg, Tricbomonas vaginalis, Entamoeba bistolytica, Giardia duodenalis), a wide range of clinically significant anaerobic bacteria (eg, Bacteroides fragilis, Clostridium difficile), and the microaerophilic bacterium Helicobacter pylori. In susceptible protozoal and bacterial cells, tinidazole is reduced to cytotoxic intermediates that covalently bind to DNA, causing irreversible damage. In human adults, tinidazole had a bioavailability of 100% and a V(d) of 50.7 L, was minimally bound to plasma protein (12%), had a plasma elimination t((1/2)) of 12.3 hours, and was eliminated primarily by hepatic metabolism (approximately 63%). Dose adjustment does not appear to be necessary on the basis of race, sex, or renal function. No data were found on the disposition of tinidazole in patients with hepatic insufficiency; therefore, use of tinidazole in patients with severe hepatic impairment (Child-Pugh class C) is not recommended. Clinical cure rates in patients with trichomoniasis, giardiasis, amebiasis, and amebic liver abscess were generally >90%. In comparative trials, tinidazole was as effective as metronidazole in the treatment of trichomoniasis and was significantly more effective than metronidazole in the treatment of giardiasis (P < 0.05) and amebiasis (P < 0.05). The most commonly reported (>1%) adverse effects included bitter taste, nausea, abdominal discomfort, anorexia, vomiting, and fatigue. The recommended dosage of tinidazole is a single dose of 2 g for trichomoniasis and giardiasis, and 2 g/d for 3 to 5 days for amebiasis. CONCLUSIONS: Tinidazole appears to be a promising agent for the treatment of trichomoniasis, giardiasis, amebiasis, and amebic liver abscess. Clinical studies are needed to evaluate the use of tinidazole against anaerobic bacteria and H pylori.
BACKGROUND:Tinidazole, a structural analogue of metrondazole, is an antiprotozoal agent that has been widely used in Europe and developing countries for >2 decades with established efficacy and acceptable tolerability. It was recently approved by the US Food and Drug Administration for the treatment of trichomoniasis, giardiasis, amebiasis, and amebic liver abscess. OBJECTIVE: This article reviews the pharmacologic and pharmacokinetic properties and clinical usefulness of tinidazole. METHODS: Relevant information was identified through a search of MEDLINE (1966-August 2005), Iowa Drug Information Service (1966-August 2005), and International Pharmaceutical Abstracts (1970-August 2005) using the terms tinidazole, Fasigyn, and nitroimidazole. RESULTS: In vitro, tinidazole exhibits activity against pathogenic protozoa (eg, Tricbomonas vaginalis, Entamoeba bistolytica, Giardia duodenalis), a wide range of clinically significant anaerobic bacteria (eg, Bacteroides fragilis, Clostridium difficile), and the microaerophilic bacterium Helicobacter pylori. In susceptible protozoal and bacterial cells, tinidazole is reduced to cytotoxic intermediates that covalently bind to DNA, causing irreversible damage. In human adults, tinidazole had a bioavailability of 100% and a V(d) of 50.7 L, was minimally bound to plasma protein (12%), had a plasma elimination t((1/2)) of 12.3 hours, and was eliminated primarily by hepatic metabolism (approximately 63%). Dose adjustment does not appear to be necessary on the basis of race, sex, or renal function. No data were found on the disposition of tinidazole in patients with hepatic insufficiency; therefore, use of tinidazole in patients with severe hepatic impairment (Child-Pugh class C) is not recommended. Clinical cure rates in patients with trichomoniasis, giardiasis, amebiasis, and amebic liver abscess were generally >90%. In comparative trials, tinidazole was as effective as metronidazole in the treatment of trichomoniasis and was significantly more effective than metronidazole in the treatment of giardiasis (P < 0.05) and amebiasis (P < 0.05). The most commonly reported (>1%) adverse effects included bitter taste, nausea, abdominal discomfort, anorexia, vomiting, and fatigue. The recommended dosage of tinidazole is a single dose of 2 g for trichomoniasis and giardiasis, and 2 g/d for 3 to 5 days for amebiasis. CONCLUSIONS:Tinidazole appears to be a promising agent for the treatment of trichomoniasis, giardiasis, amebiasis, and amebic liver abscess. Clinical studies are needed to evaluate the use of tinidazole against anaerobic bacteria and H pylori.
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