Bioequivalence studies: single vs multiple dose.

Abstract

Bioequivalence of different preparations of the same drug substance has gained considerable importance over the last few years due to increasing generic substitution. The procedure that the manufacturer of the generic test preparation has to show bioequivalence with an appropriate reference preparation is scientifically accepted and laid down in international regulations. However, the necessity of single- vs multiple-dose bioequivalence studies has not been discussed in detail with the exception of the Dutch and US guidelines on sustained-release theophylline formulations, where multiple-dose studies are specifically required. This paper compares the conclusions drawn from single- and multiple-dose studies in the same subjects and recommends appropriate pharmacokinetic characteristics.