The two-compartment recirculatory pharmacokinetic model'an introduction to recirculatory pharmacokinetic concepts

Abstract

Some limitations of traditional ("mamillary") compartmental pharmacokinetic models of anaesthetic related drugs arise from representing the blood as a central compartment. Recirculatory pharmacokinetic models overcome these limitations. It is proposed that the simplest recirculatory model has only two compartments, and that understanding the properties of this model is a useful introduction to recirculatory pharmacokinetic concepts. The compartments of the model are the lungs and the remainder of the body. The traditional rate constants (e.g. k12 and k21) are replaced by terms that include cardiac output. Drug infusion is into the lung compartment, and drug clearance is from the "body" compartment. The "total" drug concentrations can be thought of as the sum of the first-pass and recirculated drug concentrations at any time. Equations for both first-pass and total drug concentrations in arterial and mixed venous blood are presented. The effects of cardiac output and injection time on these concentrations were analysed. The first-pass arterial concentrations were shown to make a significant contribution to the total concentrations for high-clearance drugs and/or bolus drug administration. There was an inverse relationship between these first-pass concentrations and cardiac output, and a direct relationship with bolus injection rate. Thus, the total arterial concentrations are affected by these factors in these circumstances. The two-compartment recirculatory model is the simplest tool available for elaborating recirculatory pharmacokinetic concepts. The recirculatory approach may provide a conceptual framework of drug disposition that better matches the clinical experience of anaesthetists.