Evaluation of the Single- and Multiple-Dose Pharmacokinetics of Fentanyl Buccal Soluble Film in Normal Healthy Volunteers

• Published in: Journal of clinical pharmacology 2010-07, Vol.50 (7), p.785-791
• Main Authors: Vasisht, Niraj, Gever, Larry N., Tagarro, Ignacio, Finn, Andrew L.
• Format: Article
• Language: English
• Subjects: Administration, Buccal; Adult; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Analgesics, Opioid - pharmacokinetics; Analysis of Variance; Area Under Curve; Buccal; Chromatography, High Pressure Liquid; drug absorption; Electrocardiography - drug effects; Female; fentanyl; Fentanyl - administration & dosage; Fentanyl - adverse effects; Fentanyl - pharmacokinetics; Half-Life; Humans; Male; Naloxone - pharmacology; Narcotic Antagonists - pharmacology; Nonlinear Dynamics; opioids; Oximetry; pharmacokinetic; Reproducibility of Results; Tandem Mass Spectrometry; transmucosal; Young Adult
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/0091270010361354

Fentanyl buccal soluble film (FBSF) is a rapidly absorbed transmucosal formulation of fentanyl for the management of breakthrough pain in opioid‐tolerant patients with cancer. This open‐label, 3‐period, sequential dose study evaluated the dose‐to‐dose reproducibility of the pharmacokinetics of fentanyl following the administration of 600‐or 1800‐μg doses of FBSF in 12 naltrexone‐blocked, healthy adult volunteers. Subjects received 3 study treatments: single doses of 600 μg of FBSF on day 1 and day 4 and three 600‐μg doses administered at 1‐hour intervals on day 7. Plasma fentanyl concentrations were measured over a 48‐hour period after each single dose of FBSF and 72 hours after the 3‐dose regimen. Peak plasma concentrations (mean Cmax = 1.08 and 1.01 ng/mL) and overall exposure (mean AUC0–12 = 6.3 and 6.2 h·ng/mL; mean AUCinf = 9.14 and 9.60 h·ng/mL) were nearly identical after the 2 single doses (P≥ .1, all comparisons). Cmax and overall fentanyl exposure (AUCinf) increased approximately 3‐fold with the 3‐dose regimen compared with the single‐dose periods. Fentanyl plasma concentrations following single doses of FBSF were reproducible, and 3 doses administered 1 hour apart produced a tripling in exposure and maximal concentration compared with a single dose.