Figure 12-14 Pharmacokinetic simulation demonstrating the limitations of infusion regimens based on simple pharmacokinetic parameters, with fentanyl used as an example. These infusion schemes were designed to achieve a plasma fentanyl concentration of 3 ng/mL. The upper curve shows that a regimen using a loading dose based on the volume of distribution followed by a constant infusion based on clearance results in a transient period of extremely high plasma concentrations. If the same maintenance infusion is given but the loading dose is based on the volume of the central compartment, distribution of drug to the peripheral compartments causes the plasma concentration to fall below the desired level until the compartments reach steady-state concentrations, as shown in the lower curve. Cp, plasma drug concentration.