Binding of propofol to blood components: implications for pharmacokinetics and for pharmacodynamics

Aims Propofol is a widely used i.v. anaesthetic agent. However, its binding properties to blood components have not been fully studied. Methods We studied the binding of propofol to erythrocytes, to human serum and to isolated serum proteins. Because propofol bound to ultrafiltration and equilibrium dialysis membranes, we used a co-binding technique with dextran coated charcoal and with erythrocytes. Results Propofol free fraction in blood was 1.2-1.7% at total concentrations ranging from 2.80 to 179 mu M (0.5 to 32 mu g ml(-1)). Fifty percent was bound to erythrocytes and 48% to serum proteins, almost exclusively to human serum albumin. In the clinical range of concentrations (0.5-16 mu g ml(-1)) 40% of the molecules bound to erythrocytes are on the red blood cells membranes. No binding to lipoproteins occurred and binding to alpha(1)-acid glycoprotein was less than 1.5% Conclusions We conclude that hypoalbuminaemia may increase propofol free fraction particularly during prolonged administration. Since propofol is non-restrictively cleared, no change in clearance is expected to occur, and the increase in free fraction will not be compensated by a parallel increase in clearance. It is also noted that many in vitro studies used concentrations 50 to 500 times the concentration expected to be encountered in the immediate cellular environment.