The concentration-effect relationship of the respiratory depressant effects of alfentanil and fentanyl

The relative potencies of fentanyl and alfentanil for respiratory depressio n were determined in eight healthy male volunteers in a double-blinded, ran domized study with a cross-over design. The drugs were delivered by compute r-driven infusion with logarithmically ascending plasma concentrations unti l the respiratory rate reached 2/min and/or oxygen saturation decreased bel ow 85% with subjects breathing room air. Ventilation was measured with resp iratory inductive plethysmography, indirect calorimetry, and arterial blood gas analysis, and plasma drug concentrations were determined. Pharmacodyna mic modeling was performed using a fractional Emax model for minute volume and respiratory rate and the concentrations producing 50% depression (i.e., apparent 50% effective concentration [EC,,,] values) were determined. Both drugs decreased ventilation in a similar manner, and drug infusions were t erminated at mean +/- SD measured plasma concentrations of 254 +/- 88 ng/mL and 5.1 +/- 1.7 ng/mL for alfentanil and fentanyl, respectively. Alfentani l decreased minute volume from baseline by 54% +/- 19% and respiratory rate by 40% +/- 11% with EC50 values of 234 +/- 57 ng/mL and 195 +/- 101 ng/mL. The respective decreases for fentanyl were 50% +/- 11%,41% +/- 15%, and th e estimated EC,, values were 6.1 +/- 1.4 ng/mL and 3.5 +/- 1.4 ng/mL, respe ctively. Using the apparent EC50 values, the calculated potency ratio for a lfentamil:fentanyl was mean and 95% confidence interval) 1:39 (1:31-1:46) f or minute volume and 1:51 (1:34-1:68) for respiratory rate. This is analogo us to the analgesic effect studied earlier. The findings support the notion of parallel analgesic and respiratory depressant effects of alfentanil and fentanyl. Therefore equianalgesic concentrations of both drugs will lead t o equally pronounced respiratory depression.