title: Assessment of the relative potency of fentanyl buccal tablet to intravenous morphine in healthy volunteers using a thermally induced hyperalgesia pain model.
abstract: This exploratory randomized, double-blind, placebo-controlled, 5-treatment, 5-period crossover study was conducted using a thermally induced hyperalgesia pain model in 51 healthy volunteers (33 evaluable) to characterize the relative potency of fentanyl buccal tablet (FBT) versus intravenous morphine. Relative potency was assessed using the sum of pain intensity differences over 60 minutes after the application of a 43°C, 46°C, and 49°C painful stimulus following thermally induced hyperalgesia. Relative potency was also assessed by pupil diameter and responses to subjective questionnaires. The relative potency of FBT was 46.2 times that of intravenous morphine (95% confidence interval [CI], 17.6-575.3) based on the 49°C stimulus. The relative potency of FBT based on opiate-induced miosis was 44.6 (95% CI, 29.7-77.0) at 60 minutes. These results are an initial relative potency assessment and should not be considered guidance for dose-equivalent switching between agents in clinical practice.
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Saunders
authors.forename: John
authors.initials: J
authors.lastname: Messina
authors.forename: Mona
authors.initials: M
authors.lastname: Darwish
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Leary
authors.forename: Louis R
authors.initials: LR
authors.lastname: Cantilena
mesh_terms: D000278:Administration, Buccal; D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005283:Fentanyl / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005542:Forearm; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D006930:Hyperalgesia / Q000097:blood / Q000517:prevention & control*; D007275:Injections, Intravenous; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016037:Single-Blind Method; D013607:Tablets; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; D013607:Tablets; D009020:Morphine; D005283:Fentanyl