CALCULATION OF KINETIC CONSTANTS FROM BLOOD LEVELS OF DRUGS

¹ Scientific Divisions, Abbott Laboratories, North Chicago, Illinois

A statistical method of calculation has been adapted to fitting a theoretical equation to drug blood level data. This allows calculation by a least squares method of the apparent first order absorption and disappearance rates as well as the apparent specific volume of distribution. Measures of the precision with which these three constants are determined from the experimental data are also obtained.

Calculated results from mean plasma levels of pentobarbital and HT-1479 in the dog after oral solution of drug, and from individual and mean plasma levels of salicylate in man after aspirin tablets, are given. It is found that the values of the constants obtained using average plasma concentrations are similar to the average of the values of the constants determined for each individual set of data. Fitting individual curves is preferable because the values can be treated statistically to estimate the variance of the constants in a population of subjects.

The method of calculation is applicable to studies of drugs in animals and man, allowing estimation of these pharmacokinetic factors for use in determining dosage schedules and probable drug accumulation, for comparing different drugs of interest, and other applications.