Pharmacokinetics, Pharmacodynamics, and Rational Opioid Selection

TLDR

Fentanyl, alfentanil, and sufentanil differ markedly in pharmacokinetics and pharmacodynamics, and choosing among them for anesthesia requires understanding how these properties influence onset and recovery of analgesic effect. The authors used a pharmacokinetic‑pharmacodynamic model to simulate percent‑change concentration curves for fentanyl, alfentanil, and sufentanil following bolus, brief, or prolonged intravenous infusions, enabling comparison independent of potency. Simulations revealed that alfentanil is optimal for procedures longer than 6–8 h when rapid post‑infusion recovery is desired, can provide a transient peak after a single bolus, whereas sufentanil may recover faster for shorter operations, demonstrating that PK parameters alone cannot predict relative effect‑site concentration decline.

Abstract

Fentanyl, alfentanil, and sufentanil have important pharmacokinetic and pharmacodynamic differences. Selecting one of these opioid analgesics as an adjunct to general anesthesia requires appreciation of the relationship between the pharmacokinetic and pharmacodynamic characteristics of these drugs and the onset of and recovery from drug effect. Using a pharmacokinetic-pharmacodynamic model, the authors simulated the decrease in plasma fentanyl, alfentanil, and sufentanil concentration after intravenous administration by either bolus injection, brief infusion, or prolonged infusion. The percentage change in concentration, rather than absolute concentration, was simulated to permit comparison of the relative opioid concentration independently of drug potency. These computer simulations quantified the relationship between infusion duration and the time required for recovery after termination of the infusion. The analysis suggests that alfentanil is best used for operations longer than 6-8 h when a rapid decrease in effect site (i.e., biophase) opioid concentration is desired after discontinuation of the infusion. Alfentanil may also be the most appropriate drug to provide a transient peak effect after a single bolus. Although sufentanil has longer distribution and elimination half-lives than alfentanil, recovery from sufentanil infusions may be more rapid than recovery from alfentanil infusions for operations shorter than 6-8 h. These computer simulations demonstrate that simply comparing pharmacokinetic parameters (e.g., half-lives) of different drugs will not predict the relative rates of decrease in effect site concentrations after either an intravenous bolus or a continuous infusion.