Multicompartment pharmacokinetic models and pharmacologic effects

The pharmacokinetic analysis of drug concentration in the plasma versus time data on the basis of multicompartment models makes it possible to examine not only the relationship between drug concentration in the plasma (or serum) and the intensity of a pharmacologic effect, but permits also an assessment of the relationship between pharmacologic effect and the relative drug levels in other apparent compartments of the body. Experimental difficulties such as sampling and assay problems limit the precision of data obtainable in the early (distributive) phase of drug concentration decline, so that most available data tend to fit a two‐compartment rather than a more complex model. The rate constants derived from a two‐compartment analysis of drug concentration data are almost certainly not “pure” but still hybrid, though “purer” than rate constants obtained by assuming the still simpler single‐compartment open model. Suitable pharmacologic effect data, obtained at frequent intervals after drug administration, can show whether the site of action can be considered as part of a homogeneous tissue compartment (of the two‐compartment system) or if the site of action must be considered as a distinct and separate pharmacokinetic compartment. This is illustrated by actual example, using previously published data of drug concentrations in the plasma and pharmacologic effects of lysergic acid diethylamide in man.