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Pharmacokinetic evaluation of aconiazide, a potentially less toxic isoniazid prodrug
C A Peloquin1, G T James, L D Craig
1Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Study Objective:
To determine the bioavailability and renal elimination of isoniazid, acetylisoniazid, monoacetylhydrazine, diacetylhydrazine, aconiazide, and 2-formylphenoxyacetic acid.
Study Design:
Randomized, double-blind, two-period, crossover phase I study.
Setting:
Pharmacokinetics unit at a referral hospital that specializes in the treatment of mycobacterial infections.
Subjects:
Twelve healthy volunteers selected from the hospital staff.
Interventions:
Subjects received aconiazide tablets 650 mg (containing isoniazid 300 mg) and isoniazid tablets 300 mg. Blood and urine samples were collected over 24 hours after the dose.
Measurements And Main Results:
Intact aconiazide and 2-formylphenoxyacetic acid were not detected in the serum. Compared with isoniazid tablets, aconiazide's relative bioavailability (based on the area under the serum concentration-time curve) was 50.7%; its relative maximum serum concentration was 13.4%.
Conclusions:
Isoniazid is less bioavailable after aconiazide tablets than after isoniazid tablets. The optimum dose of aconiazide remains to be determined.