The roles of stereochemistry and partial areas in a parallel design study to assess the bioequivalence of two formulations of hydroxychloroquine: A drug with a very long half life

Abstract

A bioequivalence study was carried out to compare the bioavailabilities of two formulations containing racemic hydroxychloroquine. The study was based on a single phase parallel design because the enantiomers of hydroxychloroquine have very long terminal phase half lives. A group of n = 72 healthy young men were randomly assigned to receive a single dose of either test ( n = 36 subjects) or the reference ( n = 36 subjects) formulation after which serial blood samples were harvested over 77 days. The two products were found to be bioequivalent in that 90% confidence intervals fell entirely within bioequivalence limits of 80–125% for the log transformed parameters C max and AUC 4 whether calculated from non-chiral or enantioselective blood concentrations. Similarly, 90% confidence intervals for the partial areas from AUC 4 through AUC Inst all fell within 80–125%. These data suggest that enantioselective assays were not required and that blood samples need only have been harvested up to 12 h.