MEASURED CONTEXT-SENSITIVE HALF-TIMES OF REMIFENTANIL AND ALFENTANIL

Background: The context-sensitive half-time, rather than the terminal elimination half-life, has been proposed as a more clinically relevant measure of decreasing drug concentration after a constant infusion of a given duration. The context-sensitive half-time is derived from com puter modelling using known pharmacokinetic parameters. The modelled c ontext-sensitive half-time for a 3-h infusion of alfentanil is 50-55 m in and is 3 min for remifentanil, The terminal elimination half-life i s 111 min for alfentanil and 12-30 min for remifentanil. It has not be en tested whether the modelled context-sensitive half-time reflects th e true time for a 50% decrease in drug concentration or drug effect. M ethods: Thirty volunteers received a 3-h infusion of remifentanil or a lfentanil at equieffective concentrations. Depression of minute ventil ation to 7.5% ET(CO2) was used as a measure of drug effect. Minute ven tilation response was measured, and blood samples for drug concentrati on were taken during and after drug infusion. The recovery of minute v entilation (drug effect) and decrease in blood drug concentration was plotted, and the time for a 50% change was determined, Results: The me asured pharmacokinetic context-sensitive half-time for remifentanil af ter a 3-h Infusion was 3.2 +/- 0.9 min, and its pharmacodynamic offset was 5.4 +/- 1.8 min. Alfentanil's measured pharmacokinetic context-se nsitive half-time was 47.3 +/- 12 min, and its pharmacodynamic offset was 54.0 +/- 48 min. The terminal elimination half-life modelled from the volunteers was 11.8 +/- 5.1 min for remifentanil and 76.5 +/- 12.6 min for alfentanil. Conclusions The measured context-sensitive half-t imes were in close agreement with the context-sensitive half-times pre viously modelled for these drugs. The results of this study confirm th e value of the context-sensitive half-time in describing drug offset c ompared to the terminal elimination half-life.