Context-Sensitive Half-Time

Computer simulation techniques predict "context-sensitive half-time," the time necessary to achieve a 50% decrease in drug concentration after termination of a variable-length continuous infusion at a steady-state drug level ( Fig. 11-16 ).^{[325] [326]} Such simulations are intended to provide more clinically relevant meaning to pharmacokinetic parameters. The context-sensitive half-time, more modern pharmacokinetic descriptions, and computer simulations have helped clinicians to select opioids in a more rational fashion.^{[324] [325] [327]}

Alfentanil does not exhibit a more rapid 50% decrease in plasma concentration compared with sufentanil after termination of a continuous infusion for 8 hours, despite its relatively short terminal elimination half-life. In terms of pharmacokinetic theory, this surprising difference between alfentanil and sufentanil can be explained by the fact that sufentanil's pharmacokinetic model has a large, slowly equilibrating peripheral compartment that continues to fill after termination of an infusion, thus contributing to the faster decrease in sufentanil's central compartment concentration. Remifentanil has a context-sensitive half-time that is markedly shorter than those of the other fentanyl congeners.^[315] Remifentanil's context-sensitive half-time is independent of infusion duration.

In cases of very brief duration, the context-sensitive half-times for sufentanil, alfentanil, and fentanyl are

Figure 11-16 A simulation of the time necessary to achieve a 50% decrease in drug concentration in the blood (or plasma) after variable-length intravenous infusions of remifentanil, fentanyl, alfentanil, and sufentanil. (From Egan TD, Lemmens HJ, Fiset P, et al: The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers. Anesthesiology 79:881–892, 1993.)