Rate of Inactivation of Isoniazid in South IndianudPatients with Pulmonary Tuberculosis ud2. Clinical Implications in the Treatment of PulmonaryudTuberculosis with Isoniazid either Alone or in Combination with PAS

摘要

A series of studies on the rate of inactivation of isoniazid in Indian patients with pulmonaryudtuberculosis undergoing domiciliary chemotherapy with isoniazid, alone or in combinationudwith p-aminosalicylic acid, has recently been undertaken by the TuberculosisudChemotherapy Centre, Madras. In the first study, the serum isoniazid levels of the patientsudwere determined four-and-a-half hours after intramuscular administration of a standarduddose of 3 mg/kg body-weight of isoniazid and, according to whether the serum level wasud0.58 μg/ml or above, or less than 0.58 μg/ml, the patient was classified as a slow or as audrapid inactivator. The present paper describes the second of these studies, in which theudresponse to treatment of the slow and the rapid inactivators was compared. The results ofudthis investigation suggested that there might be an association between response to treatmentudand rate of inactivation of isoniazid, since the slow inactivators were more often culturenegativeudduring treatment and showed a higher proportion of individuals with bacteriologicallyudquiescent disease at I2 months and a lower proportion with radiographic deteriorationudat six months than the rapid inactivators, while the slow inactivators who deterioratedudradiographically or clinically to an extent warranting a change of treatment during the twoudyears did so later than the corresponding rapid inactivators. There was slight evidence thatudthe slow and the rapid inactivators differed in the speed of conversion to bacteriologicaludnegativity of those patients whose disease was bacteriologically quiescent at 12 months, butudno evidence that they differed in the degree of positivity of sputum specimens that wereudpositive on culture at six, nine or 12 months, or in the frequency with which the patientsudshowed moderate or greater radiographic improvement at six months.