title: Pharmacokinetic evaluation of aconiazide, a potentially less toxic isoniazid prodrug.
abstract: 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.
authors.affiliation: Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
authors.forename: C A
authors.initials: CA
authors.lastname: Peloquin
authors.forename: G T
authors.initials: GT
authors.lastname: James
authors.forename: L D
authors.initials: LD
authors.lastname: Craig
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.forename: E A
authors.initials: EA
authors.lastname: McCarthy
authors.forename: D
authors.initials: D
authors.lastname: Iklé
authors.forename: M D
authors.initials: MD
authors.lastname: Iseman
mesh_terms: 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
chemical_list: D000995:Antitubercular Agents; C028354:aconiazide; D007538:Isoniazid