Pharmacokinetic evaluation of aconiazide, a potentially less toxic isoniazid prodrug.
OBJECTIVE
To determine the bioavailability and renal elimination of isoniazid, acetylisoniazid, monoacetylhydrazine, diacetylhydrazine, aconiazide, and 2-formylphenoxyacetic acid.


METHODS
Randomized, double-blind, two-period, crossover phase I study.


METHODS
Pharmacokinetics unit at a referral hospital that specializes in the treatment of mycobacterial infections.


METHODS
Twelve healthy volunteers selected from the hospital staff.


METHODS
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.


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.
Peloquin
C A
CA
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
James
G T
GT
Craig
L D
LD
Kim
M
M
McCarthy
E A
EA
Iklé
D
D
Iseman
M D
MD
D000328:Adult; D000995:Antitubercular Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001682:Biological Availability; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D000995:Antitubercular Agents; C028354:aconiazide; D007538:Isoniazid