Background and objectives: Fentanyl buccal soluble film (FBSF) is a small, bilayered, water-soluble polymer film (BioErodible MucoAdhesive; BEMA™) that adheres to the buccal mucosa and rapidly delivers fentanyl into the systemic circulation. It is approved for the treatment of cancer breakthrough pain in adult opioid-tolerant patients. The objective of this study was to evaluate the dose proportionality of the pharmacokinetics of FBSF in healthy subjects across a range of doses.
Methods: This was a phase I, open-label, single-dose, three-period, Latin-square crossover study in which 12 healthy subjects received single FBSF doses of 200, 600 and 1200 μg with 72 hours between doses. Oral naltrexone was administered to each subject prior to and after each study dose. Serial venous blood samples were collected for 48 hours after study drug administration. Adverse events were recorded throughout the study. Dose linearity was examined using a power model (P = a × Doseb), where P represents the dependent variable (maximum plasma drug concentration [C(max)], area under the plasma concentration-time curve [AUC] from time zero to time of the last measurable concentration [AUC(last)], or AUC from time zero to infinity [AUC(∞)]), and a and b are constants. A value of b≈1 indicated linearity.
Results: Following administration of FBSF doses of 200-1200 μg, mean C(max) values increased in a linear manner with values ranging from 0.383 ng/mL to 2.19 ng/mL, respectively. Mean AUC(last) values increased from 3.001 ng·h/mL to 19.17 ng·h/mL and mean AUC(∞) increased in a linear manner from 3.456 ng·h/mL to 20.43 ng·h/mL. All reported adverse events were considered to be mild to moderate in severity.
Conclusions: This study demonstrates that peak fentanyl plasma concentrations and overall exposure increase in a dose-proportional manner following administration of FBSF.