Establishment of a reference formulation for bioequivalence assessment of rifampicin-containing FDCs: an essential step towards improving tuberculosis treatment.Int J Tuberc Lung Dis. 2005 Jul; 9(7):791-6.IJ
Selection of a reference product for bioequivalence studies of rifampicin (RMP) in prequalifying fixed-dose combinations (FDC) for worldwide distribution through the WHO is critical.
To investigate the feasibility of establishing FDC formulations as reference products for bioequivalence studies of RMP in prequalification programmes.
A biostudy was conducted as an open, two-period randomised cross-over trial. Two three-drug FDCs containing RMP, isoniazid and ethambutol hydrochloride were administered to a group of 22 volunteers with a wash-out period of 1 week. Plasma samples were collected and analysed for the concentration of RMP and desacetyl-RMP, a major active metabolite of RMP, up to 24 h. Pharmacokinetic parameters of RMP were calculated: Cmax, AUC0-24, Tmax, kel and absorption efficiencies.
No significant difference was observed between the administered formulations with respect to the major pharmacokinetic parameters Cmax, Tmax and AUC0-24 when evaluated by parametric (two-way ANOVA) and non-parametric (Hauschke's analysis) statistical analysis. The concentration of RMP falls within the reported acceptable therapeutic range.
FDCs can be developed as a reference product for bioequivalence studies.