Indications
Metronidazole is primarily indicated for the treatment of confirmed trichomoniasis caused by Trichomonas vaginalis, excluding·he first trimester of pregnancy, as well as for treating·hese anaerobic infections may involve skin and skin structures, the abdomen, heart, reproductive organs, central nervous system, and respiratory system, and can also manifest in the bloodstream, as in septicemia cases. Common infections addressed by metronidazole include those caused by Bacteroides, Clostridium, Fusobacterium, Peptococcus, and Peptostreptococcus species. In its topical formulations, metronidazole is indicated for managing·he treatment of Crohn's disease, prophylactic use following·helicobacter pylori infection, prevention of preterm births, and treating·harmacodynamics
Metronidazole exhibits both antibacterial and antiprotozoal properties, effectively treating·homoniasis, and giardiasis. It is particularly efficacious against a rang·howing·however, metronidazole does not demonstrate significant activity against facultative anaerobes or obligate aerobes in vitro. The nitro group reduction by anaerobic organisms is believed to be responsible for metronidazole's antimicrobial cytotoxic effects, leading·he risks associated with its use, including·heral neuropathy and convulsions, particularly at higher doses. Metronidazole has shown carcinogenic potential in animal studies, though its relevance in humans remains uncertain. Therefore, it should be administered only when clinically necessary and according·hen administered orally, with a bioavailability exceeding·he maximum concentration (Cmax) rang·hieved within 25 minutes to 4 hours. The area under the curve (AUC) after a 500 mg oral dose is reported as 122 ± 10.3 mg/L·h. Intravenous administration of a 1.5 g dose results in a peak concentration of 30-40 mg/L within 1 hour, while a regimen of 500 mg administered three times daily intravenously reaches steady-state concentrations within approximately 3 days, with an observed peak concentration of 26 mg/L. Topical applications of metronidazole result in minimal systemic absorption; after applying·h only 0.1% to 1% of the dose recovered in urine and feces.
Metabolism
Metronidazole undergoes extensive hepatic metabolism through hydroxylation, oxidation, and glucuronidation pathways, generating·he primary active metabolite is 1-(2-hydroxy-ethyl)-2-hydroxymethyl-5-nitroimidazole. Both unchang·he urine, metronidazole metabolites are predominantly products of side-chain oxidation and subsequent glucuronide conjugation, with only 20% of the excreted dose appearing·hang·he major oxidative metabolites include hydroxy and acetic acid derivatives.
Mechanism of Action
Metronidazole's precise mechanism of action is not entirely elucidated, but it may involve the formation of an intermediate, generated exclusively by anaerobic bacteria and protozoa, that interacts with deoxyribonucleic acid and electron-transport proteins, subsequently inhibiting nucleic acid synthesis. Upon administration, metronidazole diffuses passively into cells. Inside the cell, its nitro group is reduced to nitro radicals by ferredoxin or flavodoxin. The electron transport chains of anaerobic or microaerophilic microorganisms exhibit a suitable redox potential, thereby making metronidazole selectively active against these organisms. This reduction process results in the formation of toxic metabolites such as N-(2-hydroxyethyl) oxamic acid and acetamide, which have the potential to damage the DNA of replicating pathogens.
