Intravenous fentanyl kinetics

Fentanyl is considered to be a short‐acting narcotic analgesic but prolonged and recurrent ventilatory depression has been reported. We examined fentanyl kinetics and excretion in 7 healthy male subjects who were given a 3.2‐ or 6.4‐μg/kg dose of 3H‐fentanyi intravenously. Arterial blood and urine samples were analyzed for unchanged fentanyl and total radioactivity. Fentanyl concentrations fell rapidly and 98.6% of the dose was eliminated from plasma in 60 min but the terminal elimination phase of fentanyl from the body was slow (t½β = 219 min) due to the slow return of the unchanged drug from a peripheral compartment to the central compartment where elimination occurred primarily by biotransformation. Eighty‐five percent of the dose was recovered in urine and feces in 72 hr; less than 8% was recovered as unchanged fentanyl. There were fluctuations in plasma fentanyl levels during the elimination phase in all cases. The long t½β and fluctuations in plasma levels may contribute to prolonged and recurrent ventilatory effects of fentanyl.