THE EXTENSION GRADE - A MODEL-UNSPECIFIC RATE CHARACTERISTIC DERIVED FROM STEADY-STATE PLASMA-LEVEL FLUCTUATIONS

The rate aspect of bioavailability for pharmaceutical dosage forms in general and sustained-release preparations in particular can be quanti fied by an extension grade (EG), which is readily computed from steady -state data after administration of a test product and a suitable refe rence. Although the EG is unrelated to specific pharmacokinetic models or statistical moment analysis, interindividual differences of dispos ition kinetics are properly accounted for. It characterizes drug input in its entirety (i.e., the combination of drug release and absorption kinetics) and assumes values in the interval {0, 1}. Its properties r esemble in several respects those of the area under the concentration versus time curve quotient F, which indicates the extent of bioavailab ility. The EG can be calculated from steady-state plasma levels and ur inary excretion rates and from corresponding profiles observed after a dministration of single doses. It is easy to implement specific experi mental designs for the determination of the EG.