Rate of Inactivation of Isoniazid in South IndianudPatients with Pulmonary Tuberculosis: 1.Microbiological Assay of Isoniazid in Serumudfollowing a Standard Intramuscular Dose

摘要

Since isoniazid is metabolized in man to several derivatives with little or no specificudactivity against the tubercle bacillus, its rate of inactivation in the body may have an importantudbearing on its efficacy as an antituberculosis drug. The inactivation rate, thoughudconstant in any one person, is known to vary from individual to individual and fromudrace to race. A series of studies on the rate of inactivation of isoniazid in Indian patientsudwith pulmonary tuberculosis has recently been undertaken at the Tuberculosis ChemotherapyudCentre, Madras. The present paper describes the first of these studies, in which theudconcentration of isoniazid in the serum of patients admitted to a controlled comparison ofudfour domiciliary chemotherapeutic regimens was determined by microbiological assayudfour-and-a-half hours after administration of a standard dose of isoniazid (3 mg/kgudbody-weight). Patients with serum levels of 0.58 μg/ml or more were classifiedudas slow inactivators of isoniazid and those with levels below 0.58 μg/ml as rapidudinactivators. By this definition, 195 (61%) of the 321 patients studied were found toudbe slow inactivators and 126 (39%) rapid inactivators. A relationship was shownudbetween sex and the rate of inactivation, there being a significantly higher proportionudof rapid inactivators among the females than among the males. The observedudestimates, of the error of the microbiological assay procedure are discussed and possibleudways of reducing the error suggested.