PHARMACOKINETIC EVALUATION OF ACONIAZIDE, A POTENTIALLY LESS TOXIC ISONIAZID PRODRUG

Study Objective. To determine the bioavailability and renal eliminatio n of isoniazid, acetylisoniazid, monoacetylhydrazine, diacetylhydrazin e, aconiazide, and 2-formylphenoxyacetic acid. Study Design. Randomize d, double-blind, two-period, crossover phase I study Setting. Pharmaco kinetics unit at a referral hospital that specializes in the treatment of mycobacterial infections. Subjects. Twelve healthy volunteers sele cted from the hospital staff.-Interventions. Subjects received aconiaz ide tablets 650 mg (containing isoniazid 300 mg) and isoniazid tablets 300 mg. Blood and urine samples were collected over 24 hours after th e dose. Measurements and Main Results. Intact aconiazide and 2-formylp henoxyacetic acid were not detected in the serum. Compared with isonia zid tablets, aconiazide's relative bioavailability (based on the area under the serum concentration-time curve) was 50.7%; its relative maxi mum serum concentration was 13.4%. Conclusions. Isoniazid is less bioa vailable after aconiazide tablets than after isoniazid tablets. The op timum dose of aconiazide remains to be determined.