The WHO simplified study protocol in practice: investigation of combined formulations supplied by the WHO

SETTING: The benefits of fixed-dose combination (FDC) formulations of rifam picin, isoniazid and pyrazinamide over individual formulations are well rec ognised. OBJECTIVES: To evaluate the comparative bioavailability of antituberculosis drugs in FDC formulations and the same doses in separate formulations of a ntituberculosis drugs, using a simplified protocol developed by the World H ealth Organization (WHO). METHODS: Twenty healthy volunteers were included in the study and evaluated for bioequivalence of rifampicin in a cross-over experimental design. Afte r administration of drugs the plasma concentration of rifampicin and desace tyl-rifampicin was measured repeatedly up to 8 hours in both plasma and uri ne. Various pharmacokinetic parameters of rifampicin, such as C-max, T-max, elimination rate constant, area under the curve (AUC) up to 8 hours and ab sorption efficiency were calculated. RESULTS: No significant differences were observed between the FDCs and sepa rate formulations when C-max, T-max, AUC and absorption efficiencies were c ompared by parametric test and Hauschke's analysis. CONCLUSION: The WHO simplified protocol is suitable for evaluating bioequiv alence of antituberculosis drugs.