Relative bioavailability of isoniazid in a fixed-dose combination product in healthy Mexican subjects

• Published in: The international journal of tuberculosis and lung disease Vol. 18; no. 1; pp. 49 - 54
• Main Authors: Milán-Segovia, R. C., Vigna-Pérez, M., Romero-Méndez, M. C., Medellín-Garibay, S. E., Vargas-Morales, J. M., Magaña-Aquino, M., Romano-Moreno, S.
• Format: Journal Article
• Language: English
• Published: Paris, France International Union Against Tuberculosis and Lung Disease 01-01-2014; International Union against Tuberculosis and Lung Disease
• Subjects: Administration, Oral; Adult; Antitubercular Agents - administration & dosage; Antitubercular Agents - blood; Antitubercular Agents - pharmacokinetics; Area Under Curve; Bacterial diseases; Biological and medical sciences; Biological Availability; Cross-Over Studies; Drug Combinations; Drugs, Generic - administration & dosage; Drugs, Generic - pharmacokinetics; Fdcs; Female; Half-Life; Healthy Volunteers; Human bacterial diseases; Humans; Infectious diseases; Inh; Isoniazid - administration & dosage; Isoniazid - blood; Isoniazid - pharmacokinetics; Male; Medical sciences; Metabolic Clearance Rate; Pneumology; Pyrazinamide - administration & dosage; Relative Bioavailability; Rifampin - administration & dosage; Therapeutic Equivalency; Tuberculosis and atypical mycobacterial infections; Young Adult; Central America; Mexico; America; relative bioavailability; INH; Healthy subject; Respiratory disease; Product; Mycobacterial infection; Bioavailability; Posology; FDCs; TB; Infection; Tuberculosis; Bacteriosis; Antituberculous agent; Antibacterial agent; Dose; Isoniazid
• ISSN: 1027-3719; 1815-7920
• DOI: 10.5588/ijtld.13.0266

SETTING: 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.DESIGN: 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), AUC0-24h and AUC0-∞ 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.