Pharmacokinetic model for simultaneous determination of drug levels in organs and tissues.

An extension of the Bischoff-Dedrick pharmacokinetic model is presented. This model is derived from basic considerations of drug distrubition with physiological and anatomical meaning. The Bischoff-Dedrick model can simultaneously predict drug distribution with time in blood, organs, and tissues of pharmacological interest. The parameters are applied to a 15-kg standard dog. The experimental kinetic data of thiopental in brain, plasma, liver, lean tissue, and adipose tissue in a dog are used to demonstrate the feasibility of the model. Allowable variations in the parameters are determined. In general, the kinetics of drug distribution in blood, organs, and tissues depend on the drug dosage, lipid solubility, partition coefficients, metabolism rate, excretion rate, protein binding, route of administration, sizes of organs and tissues, and blood flow rates through organs and tissues. These factors enter the kinetic model separately and explicitly so their effects on the kinetics of drug distribution can be studied to provide valuable information for optimal therapy.