The Utility of Steady State Trough Concentrations in Assessing Intrasubject Variability

Abstract

During drug development, trough concentrations are usually monitored following repeated dosing to ensure that steady state has been achieved. Further utility of this information is explored in the estimation of intrasubject variability. Intrasubject variability is essential to the determination of sample sizes for planning within-subject (ie, crossover) studies of the effects of meals, concomitant drugs, or formulation changes (ie, bioequivalence). The utility of steady state trough concentration was evaluated as an indicator of intrasubject variability compared to a conventional approach of using a fraction of intersubject variability and to estimates obtained directly from crossover studies. Based on available data, estimates of intrasubject variability by the trough concentration approach were comparable to those from the other two approaches.