Klinické studie
Pharmacokinetics, efficacy, and tolerability of fentanyl following intranasal versus intravenous administration in adults undergoing third-molar extraction: A randomized, double-blind, double-dummy, two-way, crossover study
Lona L. Christrup PhD1, Corresponding Author Contact Information, E-mail The Corresponding Author, David Foster PhD2, Lars D. Popper PhD3, Tine Troen MSc4 and Richard Upton PhD5
1Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark
2Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
3Department of Medical Scientific Strategy and Medical Marketing, Nycomed Pharma, Roskilde, Denmark
4Department of Biostatistics, Nycomed Pharma, Roskilde, Denmark
5Discipline of Anaesthesia and Intensive Care, Royal Adelaide Hospital, The University of Adelaide, Adelaide, Australia
Abstract
Objective: The aim of this study was to compare the pharmacokinetic profile, as well as the efficacy and tolerability, of IN and IV administration of fentanyl in acute, episodic pain in patients undergoing third-molar extraction.
Methods: In this randomized, double-blind, double-dummy, 2-way, crossover study, patients were randomized to receive 1 of 4 doses (75, 100, 150, or 200 μg) by both the IN and IV routes in random order, after each of 2 separate molar extractions (interval, ≥1 week). Venous blood samples were obtained for quantification of plasma fentanyl concentrations before and at 1, 3, 5, 7, 9, 12, 15, 25, 40, 60, 90, 120, and 180 minutes after administration. Pain scores (on an 11-point numeric rating scale) were recorded before and at 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, and 240 minutes. Patients indicated the times at which they perceived meaningful pain relief (onset of action) and at which analgesia ended (duration of effect), after which they were able to use rescue medication (time to rescue medication use).
Results: A total of 24 patients were enrolled (in all, 47 extractions) (46% male; mean age, 24.1 years; 94% white, 6% Asian). Mean Tmax values were 12.8 and 6.0 minutes (P < 0.001), times to onset of analgesia were 7 and 2 minutes (P < 0.001), and durations of effect were 56 and 59 minutes after IN and IV administration (P = NS), respectively. Differences in the onsets and durations of analgesia after IN and IV administration of single doses were not significantly different, and neither was the difference in overall analgesia, with pain scores returning to near-predose values at statistically similar times after dosing. Duration of effect was directly related to IN fentanyl dose, with significantly less use of rescue medication after IN than after IV administration (P < 0.005). The IN and IV formulations were both well tolerated, with similar numbers of nasally related adverse events recorded for both routes of administration.
Conclusions: Onsets and durations of analgesia were not significantly different between single doses of IN and IV fentanyl in these adults undergoing third-molar extraction. Both IN and IV administration were generally well tolerated.
Clinical Therapeutics, Volume 30, Issue 3, March 2008, Pages 469-481
