The Biophase Concept and Intravenous Anesthesia Donald R. Stanski, M.D. and Steven L. Shafer Palo Alto, California Lecture Objectives: To introduce clinicians to the essential role of the biophase in understanding the relationship between concentration and response, and thus the relationship between drug dose and drug response. Plasma-Effect Site Equilibration: Although the plasma concentration following an intravenous bolus peaks nearly instantaneously, no anesthesiologist would induce a patient with an intravenous bolus of a hypnotic and immediately intubate the patient. The reason, of course, is that although the plasma concentration peaks almost instantly, additional time is required for the drug concentration in the brain to rise and induce unconsciousness, as shown in figure 1. This delay between peak plasma concentration and peak concentration in the brain is called hysteresis. Hysteresis is the clinical manifestation of the fact that the plasma is usually not the site of drug action, only the mechanism of transport. Drugs exert their biological effect at the “biophase,” also called the “effect site,” which is the immediate milieu where the drug acts upon the body, including membranes, receptors, and enzymes. The concentration of drug in biophase cannot be measured. First, it is usually inaccessible, at least in human subjects. Second, even if we could take tissue samples, the drug concentration in the microscopic environment of the receptive molecules will not be the same as the concentration grossly measured in, say, ground brain or CSF. Although it Figure 1 : The plasma (solid) and biophase concentrations (dashed lines) following a bolus of 3 common opioids.
is not possible to measure drug concentration in the biophase, using rapid measures of drug effect we can characterize the time course of drug effect. Knowing the time course of drug effect, we can characterize the rate of drug flow into and from the biophase. Knowing these rates, we can characterize the drug concentration in the biophase in terms of the steady state plasma concentration that would produce the same effect. Starting with the 3 compartment model introduced by Dr. Shafer in his presentation, we can now
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- Summer '07
- propofol, plasma concentration, effect site