The clinical pharmacology of alfentanil.

Alfentanil has a different pharmacokinetic and pharmacodynamic profile compared to fentanyl. Alfentanil is approximately five to eight times less potent than fentanyl when given as a single i.v. dose. The onset of alfentanil effect is five to six times more rapid than fentanyl because of a more rapid blood: brain equilibration. The rapid dissipation of alfentanil's effect occurs due to both redistribution from the brain to other tissues and rapid elimination from the body, secondary to the short elimination half-life. The short alfentanil elimination half-life arises from the marked reduction in steady-state distribution volume from a limited tissue distribution. Higher plasma concentrations are needed for endotracheal intubation and skin incision than skin closure and post-operative ventilation. Upper abdominal surgical procedures require higher plasma concentrations than lower abdominal or breast surgery. Optimal alfentanil anaesthesia occurs when plasma concentrations are maintained relatively constant at therapeutic values using infusion techniques. Age and hepatic disease alter alfentanil pharmacokinetics. Age and other CNS depressants can lower the alfentanil plasma concentrations needed for adequate clinical anaesthesia. In spite of adjusting for these factors that affect alfentanil pharmacokinetics and pharmacodynamics, unexplained pharmacokinetic variability of 30-50% exists. Alfentanil infusions must be titrated and adjusted in each patient, based upon the clinical response to circumvent this pharmacokinetic and pharmacodynamic variability.