Stability of isoniazid, rifampin and pyrazinamide in suspensions used for the treatment of tuberculosis in children

Abstract

The stability of monosuspensions, cosuspensions and multisuspensions of isoniazid (INH), pyrazinamide (PZA) and rifampin (RIF) has been evaluated by high pressure liquid chromatography over a period of 28 days both with and without the addition of vitamin C (20 micrograms/ml) and at ambient temperatures of 4 degrees C, 24 degrees C and 40 degrees C. At the end of 28 days greater than 90% of initial concentrations of INH, PZA and RIF in monosuspensions remained unchanged irrespective of ambient temperature as was the case with INH and PZA in cosuspension. The addition of RIF to either INH or PZA in cosuspension or together in multisuspension led to a marked fall in the concentration of one or more of the agents, an effect that was accentuated by the addition of vitamin C. In the case of a multisuspension of INH + RIF + PZA with vitamin C added, 41.7% (4 degrees C), 24.1% (24 degrees C) and 20.3% (40 degrees C) of initial INH concentrations and 1.9% (4 degrees C), 1.3% (24 degrees C) and 0.0% (40 degrees C) of initial RIF concentrations remained detectable after 28 days. The addition of vitamin C to monosuspensions of INH and PZA led to a marked decline in the amount of drug detectable and only in the case of RIF was greater than 90% of initial concentrations of the drug detectable after 28 days. The dispensing of cosuspensions or multisuspensions of antituberculosis agents containing RIF is inadvisable as is the addition of vitamin C in any form.