Nitrofurantoin - Pharmacology

Pharmacology

Organisms are said to be susceptible to nitrofurantoin if their minimum inhibitory concentration (MIC) is 32 μg/mL or less. The peak blood concentration of nitrofurantoin following an oral dose of nitrofurantoin 100 mg, is less than 1 μg/mL and may be undetectable; tissue penetration is negligible; the drug is well concentrated in the urine: 75% of the dose is rapidly metabolised by the liver, but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/ml or more. For this reason, nitrofurantoin cannot be used to treat anything other than simple cystitis.

At the concentrations achieved in urine (>100 microgm/mL), nitrofurantoin is bacteriocidal. It is bacteriostatic against most susceptible organisms at concentrations less than 32 micrograms per milliliter.

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 60 mL/min or less. However a retrospective chart review may suggest that nitrofurantoin is not contraindicated in this population.