Estimation of pharmacokinetic parameters in extravascular multiple dose administration in the one-compartment open body model with equal absorption and elimination first-order rate constants

Abstract

where Cb is the drug concentration in the body, D is the dose administered, F is the fraction of the dose absorbed, V is the apparant volume of distribution, t is the time and k is the absorption or elimination rate constant. Eqn. 1 describes the concentration of the drug in the body after a single dose administration. In this case the general Bateman equation (Eqn. 2) (Dost, 1968) is indeterminable and therefore cannot be used to estimate the relevant pharmacokinetic parameters. (Dost, 1968; Gibaldi and Perrier 1975a; Bialer, 1980). Furthermore, because absorption continues throughout the elimination phase, the terminal slope of log Cb vs t plot is not linear and therefore cannot be used to determine a rate constant or the extrapolated Cb* (extrapolated drug concentration in the body at time zero). Obviously, the method of residuals (the ‘feathering’ technique) cannot be used. Cb FDka(e”-k” ,-k*“) .?L V(ka ke) (2)