Bioequivalence of isoniazid in a two drug fixed dose combination and in a single drug dosage form

To increase the patient compliance and reduce the risk of drug resistant st rains, WHO and IUATLD recommend the use of Fixed Dose Combination (FDC) tab lets as a routine therapeutic regimen in Directly Observed Treatment Shortc ourse (DOTS). But the main issue in the use of FDC is the quality of the fo rmulation. At present WHO and IUATLD suggest the bioequivalence assessment of only rifampicin from FDC compared to separate formulations. For the ther apeutic effectiveness all the components of the FDCs should be bioavailable at tissue site. Also, the primary and acquired resistance rate of isoniazi d is much higher compared to other anti-tubercular drugs. Hence, a comparat ive bioavailability study of isoniazid from a two drugs FDC compared to a s eparate formulation was carried out on a group of 12 healthy volunteers. Wh en evaluated by normal or log transformed confidence interval, Two Way ANOV A and Hauschke analysis, the bioequivalence limits for AUC(0-8) and AUC(0-2 4) were within 0.8-1.25. For C-max and T-max, these limits were within 0.7- 1.43. Hence, isoniazid from a FDC formulation was found to be bioequivalent to a separate formulation at same dose levels.