Estimation of absolute bioavailability assuming steady state apparent volume of distribution remains constant

Abstract

The limitations of using estimates of extent of bioavailability (F) based on the assumption that either clearance (CL) or V_area remain, constant are discussed in relation to the situation where CL changes between doses. When estimates of F assume CL to remain constant, the entent of the error is the same for all drugs where the percentage change in CL is the same. Assuming V_area to remain constant, the error in F will vary between drugs for similar percentage changes in CL and is related to the extent to which the kinetics of the disposition process deviate from a one compartment body model. A noncompartmental method is described where, provided the reference dose is given intravenously, F can be estimated based on the assumption that V_ss remains constant between doses. This method is more accurate than those based on the assumption that either CL or V_area remain, constant when CL changes between doses, but is subject to error when the terminal loglinear slope of Cp vs. time better reflects the process of absorption rather than elimination.