Bioavailability calculations for drugs showing simultaneous first-order and capacity-limited elimination kinetics

A method is proposed for determining the bioavailability of drugs whose elimination from a one-compartment body model occurs by one or more apparent first-order processes in parallel with one capacity-limited elimination process. Plasma concentration-time data obtained after intravenous administration of the drugs are necessary to calculate the equation parameters (K1, Km,and Vm)needed to measure the extent of absorption after oral administration and to calculate the absorption rate constant using a modified Wagner-Nelson equation. Using simulated C,tdata,it is shown that the error involved in calculating the fraction of a dose absorbed after oral administration by assuming linear kinetics is a function of the absorption rate constant and the extent of absorption.