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• W2157776766 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 delayed mean fentanyl time to maximum concentration (13 vs 6 min) and lower maximum concentration (1.2 vs 2.0 ng/mL). Analgesic effect lagged behind the venous fentanyl concentration, with a half-life of approximately 2.5 minutes as described by a fractional sigmoid maximum drug effect dynamic model. The concentration-analgesia relationship was steep, with a 50% effective concentration of 0.46 ng/mL (Hill coefficient 3.5). Intranasal onset and offset of analgesia were slightly delayed, principally due to the delay and lag in systemic absorption, with slightly lower peak analgesic effect, compared with intravenous fentanyl. Duration of effect was directly related to intranasal fentanyl dose, with pain scores returning to predose values at approximately 120 minutes (75 microg) to approximately 240 minutes (200 microg) after a single dose.Intranasal fentanyl showed kinetic and dynamic properties that are desirable for the management of acute, episodic (breakthrough) pain." @default.
• W2157776766 created "2016-06-24" @default.
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• W2157776766 date "2008-08-26" @default.
• W2157776766 modified "2023-10-01" @default.
• W2157776766 title "Pharmacokinetics and Pharmacodynamics of Intranasal Versus Intravenous Fentanyl in Patients with Pain after Oral Surgery" @default.
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• W2157776766 doi "https://doi.org/10.1345/aph.1l168" @default.
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