History of pharmacokinetics.

The term pharmacokinetics was first introduced by F. H. Dost in 1953 in his text, Der BliitspiegeI-Kinetic der Konzentrationsablaiife in der Frieslauffliissigkeit (Dost, 1953). However, some of the subject matter was published before the word was coined. It is also of interest that the first English language review of the subject matter, published in 1961, was entitled the Kinetics of Drug Absorption, Distribution, Metabolism and Excretion and did not include the word pharmacokinetics (Nelson, 1961). Pharmacokinetics has been defined in a number of ways. Literally, the word means the application of kinetics to pharmakon, the Greek word for drugs and poisons. Kinetics is that branch of knowledge which involves the change of one or more variables as a function of time. The purpose of pharmacokinetics is to study the time course of drug and metabolite concentrations or amounts in biological fluids, tissues and excreta, and also of pharmacological response, and to construct suitable models to interpret such data. In pharmacokinetics, the data are analyzed using a mathematical representation of a part or the whole of an organism. Broadly then, the purposes of pharmacokinetics are to reduce data to a number of meaningful parameter values, and to use the reduced data to predict either the results of future experiments or the results of a host of studies which would be too costly and time-consuming to complete (Wagner, 1968 and 1975). A similar definition has been given by other authors (Gibaldi and Levy, 1976) as follows: 'Pharmacokinetics is concerned with the study and characterization of the time course of drug absorption, distribution, metabolism and excretion, and with the relationship of these processes to the intensity and time course of therapeutic and adverse effects of drugs. It involves the application of mathematical and biochemical techniques in a physiologic and pharmacologic context.' In this historical review emphasis is placed on pharmacokinetic theory and not on applications of that theory.