Cycloserine

Cycloserine inhibits cell wall synthesis (by competing with D-alanine for incorporation into the cell wall) in susceptible strains of Gram-positive and Gram-negative bacteria and in Mycobacterium tuberculosis.

Cycloserine is indicated in the treatment of active pulmonary and extra-pulmonary tuberculosis (including renal disease) when the organisms are susceptible to this drug and after failure of adequate treatment with the primary medications (streptomycin, isoniazid, rifampicin and ethambutol). Like all anti-tuberculous drugs, cycloserine should be administered in conjunction with other effective chemotherapy and not as the sole therapeutic agent.

Cycloserine may be effective in the treatment of acute urinary tract infections caused by susceptible strains of Gram-positive and Gram-negative bacteria, especially Klebsiella/Enterobacter species and Escherichia coli. It is generally no more and may be less effective than other antimicrobial agents in the treatment of urinary tract infections caused by bacteria other than mycobacteria. Use of cycloserine in these infections should be considered only when the more conventional therapy has failed and when the organism has been demonstrated to be sensitive to the drug.

Cycloserine is rapidly and almost completely absorbed from the GI tract after oral administration. Following the administration of a 250 mg dose plasma levels are detectable within an hour and peak plasma concentrations of approximately 10 mg/l are achieved 3 4 hours after dosage administration. It is widely distributed throughout body fluids and tissues.

There is no appreciable blood-brain barrier, and CSF levels are approximately the same as plasma levels. It is found in the sputum of tuberculous patients and has been detected in pleural and ascitic fluids, bile, amniotic fluid and fetal blood, breast milk, lung and lymph tissues.

Cycloserine is excreted into the urine, levels appearing within half an hour of oral ingestion. Approximately 66 per cent of a dose appears unchanged in the urine in 24 hours. A further 10 per cent is excreted over the next 48 hours. It is not significantly excreted in the faeces. Approximately 35 per cent is metabolised, but the metabolites have not yet been identified.

The half-life of cycloserine is in the range 8 12 hours.

A study in two generations of rats given doses up to 100 mg/kg/day demonstrated no teratogenic effect in offspring.