Bioavailability of rifampicin, isoniazid and pyrazinamide in a triple drugformulation: comparison of plasma and urine kinetics

SETTING: The present study assesses bioavailability indices for rifampicin, isoniazid and pyrazinamide when administered to healthy volunteers separat ely or in a fixed triple-drug formulation, Rifater 125 SCT. OBJECTIVE: To compare the pharmacokinetics of rifampicin, isoniazid and pyr azinamide based on their blood concentrations up to 12 hours with the propo rtions of the doses of the drugs and their metabolites excreted in urine up to 12 hours, and to assess the bioavailability indices for the free and fi xed triple drug formulations. DESIGN: An open cross-over study was conducted in 18 healthy volunteers wit h normal hepatic and renal functions to whom the drug combinations were adm inistered in free and fixed dose formulations a week apart, to the same sub ject. RESULTS: Concentrations of the three drugs/metabolites were assessed in blo od and urine. The results indicated the absence of negative pharmacokinetic interactions between the drugs when administered in both the free and the new fixed triple drug formulation. CONCLUSION: Human bioavailability studies provide direct straightforward in formation, particularly when studying compounds such as rifampicin and othe r major anti-tuberculosis drugs. The results of the present study indicate that the pharmacokinetic properties of rifampicin, isoniazid and pyrazinami de as assessed after individual and combined administration do not change w hen combined in a single pharmaceutical preparation. The bioavailability in dices calculated based on plasma concentrations and urinary levels for all three drugs compared well.