Rate of inactivation of isoniazid in South Indian patients with pulmonary tuberculosis.

Since isoniazid is metabolized in man to several derivatives with little or no specific activity against the tubercle bacillus, its rate of inactivation in the body may have an important bearing on its efficacy as an antituberculosis drug. The inactivation rate, though constant in any one person, is known to vary from individual to individual and from race to race. A series of studies on the rate of inactivation of isoniazid in Indian patients with pulmonary tuberculosis has recently been undertaken at the Tuberculosis Chemotherapy Centre, Madras. The present paper describes the first of these studies, in which the concentration of isoniazid in the serum of patients admitted to a controlled comparison of four domiciliary chemotherapeutic regimens was determined by microbiological assay four-and-a-half hours after administration of a standard dose of isoniazid (3 mg/kg body-weight). Patients with serum levels of 0.58 mug/ml or more were classified as slow inactivators of isoniazid and those with levels below 0.58 mug/ml as rapid inactivators. By this definition, 195 (61%) of the 321 patients studied were found to be slow inactivators and 126 (39%) rapid inactivators. A relationship was shown between sex and the rate of inactivation, there being a significantly higher proportion of rapid inactivators among the females than among the males. The observed estimates of the error of the microbiological assay procedure are discussed and possible ways of reducing the error suggested.