Comparative bioequivalence study of rifampicin and isoniazid combinations in healthy volunteers

OBJECTIVE: To assess the bioavailability of rifampicin (RMP) in three brand s of combination formulations of anti-tuberculosis drugs. DESIGN: A three-way double-blind, cross-over bioavailability study of RMP a nd isoniazid (INH), consisting of a comparison of a two-drug combination of tablets of RMP and INH each separately (reference brand R) and a tablet of RMP + INH (brand N), and a capsule of RMP + INH (brand L) was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for level s of RMP as well as INH and acetylisoniazid (ACINH) by two high performance liquid chromatography (HPLC) methods. RESULTS: The mean values of RMP in brand N (C-max 6.49 +/- 0.52 mu g/mL, T- max 2.33 +/- 0.18 h, AUC((0-24h)) 39.83 +/- 3.44 mu g/mL.h) were comparable with those obtained with brand R (C-max 5.22 +/- 0.59 mu g/mL, T-max 2.50 +/- 0.12 h, AUC((0-24h)) 33.33 +/- 3.47 mu g/mL.h). The mean values of RMP in brand L (C-max 3.05 +/- 0.52 mu g/mL, T-max 3.79 +/- 0.57 h and AUC((0-2 4h)) 21.78 +/- 3.67 mu g/mL.h) were significantly different from those in b rand R. Nevertheless, all of the pharmacokinetic parameters obtained for IN H and ACINH in all three brands were comparable. CONCLUSION: Using brand R as a comparison, brand N was bioequivalent and br and L was not bioequivalent.