PHARMACOKINETIC EVALUATION OF THIACETAZONE

Study Objective. To investigate the steady-state pharmacokinetics of t hiacetazone (TB-1), which is active in vitro against Mycobacterium avi um complex (MAC). Design. Open-label phase I study. Setting. Specializ ed referral hospital. Patients. Twelve healthy men and women. Interven tions. Oral TB-1 150 mg/day was administered for 7 days, followed by b lood and urine collection over 48 hours. Measurements and Main Results . The serum concentration versus time curves of TB-1 showed sustained concentrations, with maximum values of 1.59 +/- 0.47 mu g/ml, time to maximum 3.30 +/- 1.18 hours, and serum half-life of 15-16 hours. Less than 25% of TB-1 was recovered unchanged in the urine over 48 hours. R ashes occurred in two subjects at the end of the 7-day dosing period a nd resolved without progression or sequelae. Conclusions. Based on the se data, we initiated a phase II study of TB-l in patients with pulmon ary MAC infection who do not have the acquired immunodeficiency syndro me.