Pharmacokinetics and pharmacodynamics of intranasal versus intravenous fentanyl in patients with pain after oral surgery

The Annals of Pharmacotherapy
David FosterLars Popper

Abstract

Fentanyl, a short-acting synthetic opioid, has a pharmacokinetic profile suited to fast relief of brief episodic pain. To characterize the pharmacokinetic-pharmacodynamic correlation of intranasal and intravenous fentanyl in opioid-naïve patients undergoing third molar extraction. A double-blind, double-dummy, crossover design study was conducted, with patients randomized to receive 1 of 4 fentanyl doses (75, 100, 150, or 200 microg) by both the intravenous and intranasal routes. Venous fentanyl concentrations were determined for up to 180 minutes and pain scores were recorded up to 240 minutes postdose. Duration of effect and time to rescue medication were also recorded. The pharmacokinetics of intravenous fentanyl reflected a 2-compartment model with a clearance of approximately 1.5 L/min. There was moderate (<50%) between-subject variability (BSV; %CV [coefficient of variation]) in the systemic kinetics of fentanyl. Bioavailability of intranasal fentanyl was 89%, following first-order absorption, with a lag of approximately 5 minutes and a half-life of approximately 6.5 minutes. Interpatient absorption variability was approximately 30% BSV for all absorption parameters. Intranasal versus intravenous administration led to a d...Continue Reading

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