Nonlinear pharmacokinetics of ethanol: the disproportionate AUC-dose relationship

Whole venous blood concentrations of ethyl alcohol were measured following the constant rate intravenous infusion of ethanol to four Beagle dogs. Five different doses (0.1-0.8 g ethanol/kg body weight) were administered at scheduled intervals. The area under the blood ethanol concentration-time curves (AUC) was found to demonstrate a markedly nonlinear relationship with the administered dose. Simulations of one and two compartment open models with Michaelis-Menten elimination kinetics and zero-order input are presented with their theoretical AUC-dose relationships.