| Abstract: | Current methods of evaluating the bioavailability of drugs with nonlinear disposition kinetics are based on specific pharmacokinetic models in contrast to the more rational model independent (structureless) area under the curve (AUC) and deconvolution methods used in linear pharmacokinetics. A novel method of evaluating bioavailability is presented which applies to any nonlinear type of drug elimination, but is limited to drugs with a distribution phase which is short relative to the elimination phase. The method applies to drugs with autonomic disposition characterized by a rate of decline in the systemic drug level in the absence of drug input which depends only on the drug level, i.e., dC/dt = -q(C), where q can be any function dependent only on C and constant kinetic parameters. It is shown that the disposition function q(C) can be evaluated in an empirical fashion from elimination-phase data and that this function can be used to calculate the absolute bioavailability of autonomic, nonlinear drugs. Some preliminary results are presented to demonstrate the procedures involved in applying the method. |
