Metronidazole is of the nitroimidazole class. It inhibits nucleic acid synthesis by forming nitroso radicals, which disrupt the DNA of microbial cells. This function only occurs when metronidazole is partially reduced, and because this reduction usually happens only in anaerobic bacteria and protozoans, it has relatively little effect upon human cells or aerobic bacteria. Pharmacokinetics Oral metronidazole is approximately 80% bioavailable via the gut and peak blood plasma concentrations occur after one to two hours. Food may slow down absorption but does not diminish it. Of the circulating substance, about 20% is bound to plasma proteins. It penetrates well into tissues, the cerebrospinal fluid, the amniotic fluid and breast milk, as well as into abscess cavities. About 60% of the metronidazole is metabolized by oxidation to the main metabolite hydroxymetronidazole and a carboxylic acid derivative, and by glucuronidation. The metabolites show antibiotic and antiprotozoal activity in vitro. Metronidazole and its metabolites are mainly excreted via the kidneys (77%) and to a lesser extent via the faeces (14%). The biological half-life of metronidazole in healthy adults is eight hours, in infants during the first two months of their lives about 23 hours, and in premature babies up to 100 hours. The biological activity of hydroxymetronidazole is 30% to 65%, and the elimination half-life is longer than that of the parent compound. The serum half-life of hydroxymetronidazole after suppository was 10 hours, 19 hours after intravenous infusion, and 11 hours after a tablet. History The drug was initially developed by Rhône-Poulenc in the 1950s and licensed to G.D. Searle. Searle was acquired by Pfizer in 2003. The original patent expired in 1982, but evergreening reformulation occurred thereafter. Brand name In India, it is sold under the brand name Metrogyl and Flagyl. In Bangladesh, it is available as Amodis, Amotrex, Dirozyl, Filmet, Flagyl, Flamyd, Metra, Metrodol, Metryl, etc. In Pakistan, it is sold under the brand name of Flagyl and Metrozine. Synthesis 2-Methylimidazole (1) may be prepared via the Debus-Radziszewski imidazole synthesis, or from ethylenediamine and acetic acid, followed by treatment with lime, then Raney nickel. 2-Methylimidazole is nitrated to give 2-methyl-4(5)-nitroimidazole (2), which is in turn alkylated with ethylene oxide or 2-chloroethanol to give metronidazole (3): Veterinary use Metronidazole is used to treat infections of Giardia in dogs, cats, and other companion animals, although it does not reliably clear infection with this organism and is being supplanted by fenbendazole for this purpose