Application of physiology-based pharmacokinetic and pharmacodynamic modeling to individualized target-controlled...

This study compared the ability of the physiology-based pharmacokinetic (PBPK) model with that of compartmental models used in propofol infusion devices to predict the pharmacokinetics and pharmacodynamics of propofol in various patient groups (children, pregnant women, young men, normal weight adults, and obese adults). With a PBPK model, loss of consciousness (LOC) and recovery of consciousness (ROC) corresponded to a narrow range of brain tissue concentrations (2.2-4.0 mg/L). With the compartmental models, predicted effect concentrations were also within a narrow range at LOC, but were outside the range at ROC. In individuals of normal weight, coefficients of variation (CV) of the predicted brain or effect concentrations at LOC were in a similar range-between 18% and 32%. In obese individuals, however, interindividual CV values for brain or effect concentrations were 41% (PBPK) and 93% (compartmental). This comparison suggests the increased flexibility of PBPK models over compartmental models, the latter of which rely heavily on the patient group from which the model was derived. The incorporation of PBPK models may provide target-controlled infusions with enhanced ability to predict response in a wide variety of patients.