Pharmacokinetic evaluation of thiacetazone

Study objective: To investigate the steady-state pharmacokinetics of thiacetazone (TB-1), which is active in vitro against Mycobacterium avium complex (MAC).

Design: Open-label phase I study.

Setting: Specialized referral hospital.

Patients: Twelve healthy men and women.

Interventions: Oral TB-1 150 mg/day was administered for 7 days, followed by blood 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 micrograms/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. Rashes occurred in two subjects at the end of the 7-day dosing period and resolved without progression or sequelae.

Conclusions: Based on these data, we initiated a phase II study of TB-I in patients with pulmonary MAC Infection who do not have the acquired immunodeficiency syndrome.