title: Relative bioavailability of isoniazid in a fixed-dose combination product in healthy Mexican subjects.
abstract: METHODS
  Subtherapeutic plasma isoniazid (INH) concentrations and the development of bacterial resistance may be attributed to poor quality and reduced bioavailability of fixed-dose combination (FDC) formulations. The bioavailability of INH from a generic and that of a branded FDC formulation had not been compared in the Mexican population.
  
  
  OBJECTIVE
  To evaluate the bioequivalence of a generic three-drug FDC formulation (3FDC) in comparison with a 3FDC reference with doses of 300 mg INH in 20 healthy Mexican adults, and to generate data regarding the oral relative bioavailability of the drug in this population.
  
  
  METHODS
  A single-dose, randomised-sequence, open-label, two-period crossover study.
  
  
  RESULTS
  Both formulations were well tolerated. The pharmacokinetic parameters of INH showed wide inter-individual variability. The average relative bioavailability calculated for maximum serum concentration area under the concentration-time curve (AUC), AUC(0-24h) and AUC(0-∞) of the test 3FDC formulation vs. the 3FDC reference were respectively 64.84% (90%CI 56.01-75.06), 59.05% (90%CI 50.27-69.36) and 57.26% (90%CI 46.93-69.84).
  
  
  CONCLUSIONS
  The 3FDC test and reference formulations were not bioequivalent because the 90%CI for the geometric mean ratios did not meet the regulatory requirements for bioequivalence (range 80-125%) based on the rate and extent of absorption.
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.
authors.forename: R C
authors.initials: RC
authors.lastname: Milán-Segovia
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.
authors.forename: M
authors.initials: M
authors.lastname: Vigna-Pérez
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.
authors.forename: M C
authors.initials: MC
authors.lastname: Romero-Méndez
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.
authors.forename: S E
authors.initials: SE
authors.lastname: Medellín-Garibay
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.
authors.forename: J M
authors.initials: JM
authors.lastname: Vargas-Morales
authors.affiliation: Servicio de Infectología, Hospital Central Dr. Ignacio Morones Prieto, Servicios Coordinados de Salud, San Luis Potosí, México.
authors.forename: M
authors.initials: M
authors.lastname: Magaña-Aquino
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.
authors.forename: S
authors.initials: S
authors.lastname: Romano-Moreno
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004338:Drug Combinations; D016568:Drugs, Generic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D011718:Pyrazinamide / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D004338:Drug Combinations; D016568:Drugs, Generic; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin