The WHO simplified study protocol in practice: investigation of combined formulations supplied by the WHO.Int J Tuberc Lung Dis. 1999 Nov; 3(11 Suppl 3):S336-42; discussion S351-2.IJ
The benefits of fixed-dose combination (FDC) formulations of rifampicin, isoniazid and pyrazinamide over individual formulations are well recognised.
To evaluate the comparative bioavailability of antituberculosis drugs in FDC formulations and the same doses in separate formulations of antituberculosis drugs, using a simplified protocol developed by the World Health Organization (WHO).
Twenty healthy volunteers were included in the study and evaluated for bioequivalence of rifampicin in a cross-over experimental design. After administration of drugs the plasma concentration of rifampicin and desacetyl-rifampicin was measured repeatedly up to 8 hours in both plasma and urine. Various pharmacokinetic parameters of rifampicin, such as Cmax, Tmax, elimination rate constant, area under the curve (AUC) up to 8 hours and absorption efficiency were calculated.
No significant differences were observed between the FDCs and separate formulations when Cmax, Tmax, AUC and absorption efficiencies were compared by parametric test and Hauschke's analysis.
The WHO simplified protocol is suitable for evaluating bioequivalence of antituberculosis drugs.