Nonlinear pharmacokinetic model of intravenous anesthesia

A nonlinear pharmacokinetic model was constructed to describe the body distribution of intravenous anesthetics, using the physiological modeling approach for drug distribution kinetics. The model considers the physiological parameters of tissue volumes and blood flow rates for the standard four phases of blood, viscera, lean tissue, and adipose tissue and also the associated drug parameters known to influence drug distribution. A simple ramp function having a characteristic time (volume per flow rate) is used to describe the rate of approach to equilibrium conditions for each tissue phase. The model was evaluated for the distribution of methohexital and thiopental by comparing calculated values to experimental drug concentrations taken from the literature. The physiological alteration of obesity also was programmed into the model to evaluate its capability for predicting the influence of body alterations on drug distribution. The results indicated that a preliminary mathematical model of relatively simple design is capable of at least a semiquantitative prediction of intravenous anesthetic drug concentrations in body tissues and has the potential of accounting for differences in drug distribution in the presence of selected physiological alterations.