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 difficulty 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, crossover studies of FDCs and appropriate reference formulations.

METHOD: The results of three bioavailability and bioequivalence studies of different rifampicin-containing FDCs were analysed. The relationship between the number of time points employed and precision of estimated relative bioavailability was explored. The relative bioavailabilities of the drug components in the test FDCs were calculated using maximal concentration and area under the curve estimates 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 contracted blood sampling protocol were closely similar to those derived using the extended sampling schedules.

CONCLUSION: Considerable cost and convenience benefits can be gained by using the contracted sampling schedule with only a minor reduction in the precision of the estimation of relative rifampicin bioavailability.