Variability of fentanyl pharmacokinetics in man

The derived pharmacokinetic data for the intravenous administration of fentanyl obtained from seven previous studies were compared using computer simulation of predicted plasma concentrations following three intravenous dosage regimens. There was wide discrepancy between the reported calculated pharmacokinetic constants from the various studies, such that the volume of distribution ranged from 4.4 to 59.7 litres, estimates of terminal elimination half-life ranged from 141 to 853 minutes while total body clearance values ranged from 160 to 1530 ml/minute. The differences in predicted plasma concentrations were marked. The peak concentration following a bolus of 500 micrograms ranged from 8.4-113.6 ng/ml and took from 2.9 to 18.9 hours to fall to 0.5 ng/ml. The steady state plasma concentration reached with an infusion of 0.3 microgram/kg/minute varied from 12.2-119.9 ng/ml and the plateau level attained with a two-rate infusion (2.7 micrograms/kg/minute for 20 minutes then 0.3 micrograms/kg/minute) ranged from 10.6-50.8 ng/ml. The aim of descriptive pharmacokinetics is to allow the clinician to predict the plasma concentration achieved by a given dose and to facilitate dosage choice and adjustment. Recent interest has centred on the use of pharmacokinetics to calculate continuous intravenous infusion dosage regimens. The clinical application of current pharmacokinetic data for fentanyl is questionable.