Comparative Bioavailability of Isoniazid, Rifampin, and Pyrazinamide Administered in Free Combination and in a Fixed Triple Formulation Designed for Daily Use in Antituberculosis Chemotherapy: I. Single-Dose Study

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Abstract
A comparative bioavailability study of the antituberculosis drugs isoniazid, rifampin, and pyrazinamide was carried out in a group of 10 healthy volunteers after adminstration of the three compounds, once in individual association and once in a combined, fixed preparation. The investigation was designed as an open, crossover study where each subject received five tablets of a preparation containing 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide (corresponding to a total dose of 250 isoniazid, 600 mg rifampin, and 1,500 mg pyrazinamide). The same doses were administered in the session where the drugs were combined using the individual formulations. For each subject and experimental session, 15 blood samples were collected over a period of 24 h, and the plasma concentrations of the three drugs were assessed. The results indicated the absence of negative pharmacokinetic interactions between the drugs when administered in both free and this new, fixed combination.