Pharmacodynamic Aspects of Systemic Drug Delivery

Abstract

AbstractSome of the most common cases of drug delivery (i.v. bolus, first-order absorption and zero-order absorption) are evaluated with respect to the relationship between extent and/or rate of drug absorption and pharmacodynamic outcome. Each case is evaluated after a single dose and at steady state after multiple dosing in a one-compartment body model. The pharmacodynamic model used is the Emax-model with and without an effect compartment. The area under the effect-time curve (AUCe) is used as a cumulative measure for overall drug activity. After first-order absorption, AUCe can vary as a function of absorption rate between a minimum, the AUCE of the equivalent i.v. bolus, Emax/ke*ln[1+D/(E50*Vd)], and a maximum, Emax*D/(E50*CL). After multiple dosing, the degree of fluctuation of the pharmacodynamic effect will depend on the dose and will always be less than the degree of pharmacokinetic fluctuation. A dosing rate (DR50=CL*E50/fu) is proposed that allows calculation of the dose necessary to produce an...