A modern view of pharmacokinetics

Abstract

A modern view of pharmacokinetics must include both linear and nonlinear systems. Evidence of nonlinearities in pharmacokinetics go back to the early 1930's with the origination of the concept that ethyl alcohol is eliminated at a fixed rate independent of its concentration in the body. This paper contains references to over 160 articles which suggest evidence on nonlinearities in drug absorption, distribution, metabolism and excretion, and the pharmacokinetics of drug action. These works are reviewed in a format of six tables: Evidence for Nonlinearities in Drug Absorption; Drug Distribution; Drug Metabolism; Renal Excretion of Drugs and Metabolites; Biliary Excretion of Drugs; and Pharmacokinetics of Drug Action. Special attention is given to the equations used to describe nonlinear kinetics, the recognition of nonlinearities, nonlinear models, and the fitting of data. Seven guidelines are presented for use in possible future pharmacokinetic studies involving drug kinetics.