Choice of characteristics and their bioequivalence ranges for the comparison of absorption rates of immediate-release drug formulations
Schall, R.; Luus, H.G.; Steinijans, V.W.; Hauschke, D.
International Journal of Clinical Pharmacology and Therapeutics 32(7): 323-328
1994
ISSN/ISBN: 0946-1965 PMID: 7952792 Document Number: 428860
For immediate release drug formulations the maximum concentration (C-max), the time to the maximum concentration (t-max), and the ratio C-max/AUC have been suggested as absorption rate characteristics. Although t-max is easier to interpret as absorption rate characteristic than C-max and C-max/AUC, the latter are generally preferred in practice because these characteristics can be observed with higher precision, and are easier to handle statistically than t-max. In this paper we propose a strategy for setting appropriate bioequivalence ranges for t-max and C-max/AUC, and for choosing the best characteristic for the comparison of absorption rates when planning a bioequivalence study. This involves motivating the bioequivalence range on that scale which is most convenient for that purpose, namely in terms of differences in t-max. Exploiting the pharmacokinetic relationship between t-max and C-max/AUC this bioequivalence range is then translated into the corresponding bioequivalence range for C-max/AUC. The characteristic that gives the greatest power to show bioequivalence can then be specified as the primary absorption rate characteristic. For drugs with short elimination half-lives, or short fastest disposition half-lives if the drug concentrations follow a higher compartmental model, C-max/AUC is the best characteristic, but for drugs with long elimination or fastest disposition half-lives t-max can be superior to C-max/AUC.