Figure 1. A, The total body pharmacokinetic model describing thiopental disposition in humans. The model consists of multiple tissues and blood pools connected via the vasculature, and assumes venous injection and arterial blood sampling (Cb). The “clock” generates simulation times corresponding to the simulated blood concentrations. Regional blood flows are generated in the box in the lower right hand corner, and sum to cardiac output. Some anatomical simplifications are made. Peripheral venous injection and peripheral arterial sampling are assumed to be indistinguishable from the illustrated central venous injection and aortic sampling, after consideration of appropriate transport delays. The pancreas and spleen are represented as a common tissue. B, A typical pharmacokinetic model for an organ. Organs such as the brain or heart consist of two compartments representing vasculature and parenchyma. The rate of mass transfer between compartments is proportional to the concentration gradient; this proportionality constant is the distribution clearance. Tissue models for fat, muscle, and carcass are comprised of a single compartment which represents both vascular and parenchymal volumes. Organ models for kidney, gut, and liver require a third “deep” parenchymal compartment connected only to the “shallow” parenchymal compartment to describe prolonged retention of thiopental.