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


METHODS
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.


CONCLUSIONS
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.
McIlleron
H
H
Department of Pharmacology, University of Cape Town Medical School, Observatory, South Africa. hmciller@uctgshl.uct.ac.za
Gabriels
G
G
Smith
P J
PJ
Fourie
P B
PB
Ellard
G A
GA
D000293:Adolescent; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001800:Blood Specimen Collection; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011786:Quality Control; D012293:Rifampin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D013997:Time Factors
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D004338:Drug Combinations; D012293:Rifampin