title: Dose Proportionality and Pharmacokinetics of Fentanyl Buccal Soluble Film in Healthy Subjects : A Phase I, Open-Label, Three-Period, Crossover Study.
abstract: OBJECTIVE
  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 [Cmax], area under the plasma concentration-time curve [AUC] from time zero to time of the last measurable concentration [AUClast], 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 Cmaxvalues increased in a linear manner with values ranging from 0.383 ng/mL to 2.19ng/mL, respectively. Mean AUClastvalues increased from 3.001 ng ·/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.
authors.affiliation: BioDelivery Sciences International, Inc., 801 Corporate Center Drive, Suite 210, Raleigh, NC, 27607, USA. afinn@bdsinternational.com.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Finn
authors.affiliation: BioDelivery Sciences International, Inc., 801 Corporate Center Drive, Suite 210, Raleigh, NC, 27607, USA.
authors.forename: Niraj
authors.initials: N
authors.lastname: Vasisht
authors.affiliation: Worldwide Clinical Trials Drug Development Solutions, Austin, TX, USA.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Stark
authors.affiliation: Meda Pharmaceuticals, Inc., Somerset, NJ, USA.
authors.forename: Larry N
authors.initials: LN
authors.lastname: Gever
authors.affiliation: Meda Pharmaceuticals, Inc., Somerset, NJ, USA.|Meda Pharma S.A.U., Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Tagarro
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002610:Cheek; D018592:Cross-Over Studies; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D009061:Mouth Mucosa; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl