the dose is rapidly metabolised by the liver, but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200μg/mL or more. In studies of dogs, the majority of urinary excretion is through glomerular filtration with some tubular secretion. There is also tubular absorption which is increased with urine acidification. However the activity of nitrofurantoin is also pH dependent and mean inhibitory concentration rises sharply with increased pH above 6. Nitrofurantoin cannot be used to treat infections other than simple cystitis. At the concentrations achieved in urine (>100μg/mL), nitrofurantoin is a bactericide. It is bacteriostatic against most susceptible organisms at concentrations less than 32μg/mL. Nitrofurantoin and the quinolone antibiotics are mutually antagonistic in vitro. It is not known whether this is of clinical significance, but the combination should be avoided. Resistance to nitrofurantoin may be chromosomal or plasmid-mediated and involves inhibition of nitrofuran reductase. Acquired resistance in E. coli continues to be rare. Nitrofurantoin and its metabolites are excreted mainly by the kidneys. In renal impairment, the concentration achieved in urine may be subtherapeutic. Nitrofurantoin should not be used in patients with a creatinine clearance of 60mL/min or less. However, a retrospective chart review may suggest nitrofurantoin is not contraindicated in this population. Mechanism of action Nitrofurantoin is concentrated in the urine, leading to higher and more effective levels in the urinary tract than in other tissues or compartments. With a 100mg oral dose, plasma levels are typically less than 1µg/mL while in the urine it reaches 200µg/mL. The drug works by damaging bacterial DNA, since its reduced form is highly reactive. This is made possible by the rapid reduction of nitrofurantoin inside the bacterial cell by flavoproteins (nitrofuran reductase) to multiple reactive intermediates that attack ribosomal proteins, DNA, respiration, pyruvate metabolism and other macromolecules within the cell. Nitrofurantoin exerts greater effects on bacterial cells than mammalian cells because bacterial cells activate the drug more rapidly. It is not known which of the actions of nitrofurantoin is primarily responsible for its bactericidal activity. The broad mechanism of action for this drug likely is responsible for the low development of resistance to its effects, as the drug affects many different processes important to the bacterial cell. History Nitrofurantoin has been available for the treatment of lower urinary tract infections (UTIs) since 1953. Society and culture Brand names Nitrofurantoin is marketed under many names in countries worldwide. Animal