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

Abstract

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-microg doses of FBSF in 12 naltrexone-blocked, healthy adult volunteers. Subjects received 3 study treatments: single doses of 600 microg of FBSF on day 1 and day 4 and three 600-microg 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 C(max) = 1.08 and 1.01 ng/mL) and overall exposure (mean AUC(0-12) = 6.3 and 6.2 h.ng/mL; mean AUC(inf) = 9.14 and 9.60 h.ng/mL) were nearly identical after the 2 single doses (P >or= .1, all comparisons). C(max) and overall fentanyl exposure (AUC(inf)) 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.