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John Barnard
Waikato Clinical School, University of Auckland, Hamilton, New Zealand

Simply put, the effect site is where a drug works. The kinetics of the effect site form the dynamic link between pharmacokinetics(PK) and pharmacodynamics(PD). Typically PK data of a drug describes the relationship between the dose of a drug and its arterial plasma concentration over time. PD data describes the relationship between the arterial plasma concentration of a drug and its biological effects. At steady state the free concentration of a drug in arterial plasma is assumed to be the same as that at the effect site so the mathematics of effect site equilibria become superfluous. Unfortunately for us much of anaesthesia involves the use of drugs in non-steady state conditions. The simplest approach to modeling the effect site is to assume that the wash-in or wash-out of the effect site follows simple first order kinetics, and the interaction with the receptors follows an inhibitory Emax process. Incorporating an understanding of effect site kinetics into our clinical practice has the potential to make anaesthesia safer and more predictable, incorporating it into pump programming and monitoring opens up the potential for closed loop control of anaesthesia, and incorporating it into our research can provide insights into the mechanism of anaesthesia. All well and good in theory but anaesthesia presents some unique challenges to the champions of effect site modeling. For instance: Is anaesthesia a single state? Is there more than one effect site? What effect is the best one to measure? The answers are no, yes and I'm not sure.

Time of Presentation
Sunday 8 May 2005 - 1030-1200