Linear pharmacokinetic systems.

This paper discusses the analysis of linear, time-invariant pharmacokinetic systems. For compartmental systems, we briefly review important structural features such as strong components and traps, and methods of analysis and system identification. For noncompartmental systems, we note some properties of the impulse response, and we show that total drug exposure (Formula: see text) depends only on the total dose, and not on the rate or schedule of administration. We extend this and other laws to certain partially nonlinear systems. Finally, we note that peak drug levels usually decrease with slower rates of drug administration; but this is not necessarily true unless the impulse response is unimodal. The ratio of peak drug levels in two tissues does not necessarily increase or decrease uniformly as a function of the injection rate, but may be maximal at an intermediate injection rate.