The development of a standardised screening protocol for the in vivo assessment of rifampicin bioavailability

SETTING: The prerequisite for in vivo bioavailability testing of rifampicin in fixed-dose combination (FDC) formulations is widely accepted. However, many smaller drug regulatory authorities and drug manufacturers have diffic ulty implementing costly and cumbersome testing procedures. OBJECTIVE: TO test whether a simplified blood sampling schedule can be used for the determination of drug bioequivalence in randomised, single dose, c rossover studies of FDCs and appropriate reference formulations. METHOD: The results of three bioavailability and bioequivalence studies of different FDCs were analysed. The relationship between the number of time p oints employed and precision of estimated relative bioavailability was expl ored. The relative bioavailabilities of the drug components in the test FDC s were calculated using maximal concentration and area under the curve esti mates based on an extended blood sampling schedule of up to 15 time points over 48 hours, and a contracted sampling scheme with only six blood samples over 8 hours. RESULTS: Estimates of relative bioavailability calculated using the contrac ted blood sampling protocol were closely similar to those derived using the extended sampling schedules. CONCLUSION: Considerable cost and convenience benefits can be gained by usi ng the contracted sampling schedule with only a minor reduction in the prec ision of the estimation of relative rifampicin bioavailability.