BIOAVAILABILITY ASSESSMENT UNDER QUASI-STATE AND NONSTEADY-STATE CONDITIONS .3. APPLICATION

The applicability of bioavailability assessment at quasi- and nonsteady state is illustrated with data from a study comparing 2 formulations of amitriptyline hydrochloride in humans. Relative bioavailability as a function of the observed mean plasma concentrations may be expressed in closed form, provided the affected intervals begin and end in the log-linear region. Alternatively, numerical, graphical and/or electronic computational techniques may be used to simulate the appropriate [.hivin.Cp(i)]sim [simulated plasma concentration on the ith dosage interval] the proximity of which to [.hivin.Cp(i)]obs [observed plasma concentration on the ith dosage interval] is a function of relative bioavailability and of .omega.. If a model can be found to fit the data adequately, it would be sufficient that only 1 sampled interval end in the log-linear phase.