title: Pharmacokinetic study between a bilayer matrix fentalyl patch and a monolayer matrix fentanyl patch: single dose administration in healthy volunteers.
abstract: OBJECTIVE
  Transdermal fentanyl is a well established treatment for cancer pain. The aim of the present study is to assess the relative bioavailability of fentanyl from two different transdermal systems by evaluating plasma drug concentrations after single administration of Fentalgon® (test), a novel bilayer matrix type patch, and Durogesic SMAT (reference), a monolayer matrix type patch. In the Fentalgon patch the upper 6% fentanyl reservoir layer maintains a stable concentration gradient between the lower 4% donor layer and the skin. The system provides a constant drug delivery over 72 h.
  
  
  METHODS
  This was an open label, single centre, randomized, single dose, two period crossover clinical trial, that included 36 healthy male volunteers. The patches were applied to non-irritated and non-irradiated skin on the intraclavicular pectoral area. Blood samples were collected at different time points (from baseline to 120 h post-removal of the devices) and fentanyl concentrations were determined using a validated LC/MS/MS method. Bioequivalence was to be claimed if the 90% confidence interval of AUC(0,t) and C(max) ratios (test: reference) were within the acceptance range of 80-125% and 75-133%, respectively.
  
  
  RESULTS
  The 90% confidence intervals of the AUC(0,t) ratio (116.3% [109.6, 123.4%]) and C(max) ratio (114.4% [105.8, 123.8%] were well included in the acceptance range and the C(max) ratio also met the narrower bounds of 80-125%. There was no relevant difference in overall safety profiles of the two preparations investigated, which were adequately tolerated, as expected for opioid-naïve subjects.
  
  
  CONCLUSIONS
  The new bilayer matrix type patch, Fentalgon®, is bioequivalent to the monolayer matrix type Durogesic SMAT fentanyl patch with respect to the rate and extent of exposure of fentanyl (Eudra/CT no. 2005-000046-36).
authors.affiliation: Palliative Care, Pain Therapy and Rehabilitation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Zecca
authors.affiliation: Palliative Care, Pain Therapy and Rehabilitation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Manzoni
authors.affiliation: Palliative Care, Pain Therapy and Rehabilitation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Centurioni
authors.affiliation: Medical Affairs Department, Italfarmaco S.p.A., Cinisello Balsamo, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Farina
authors.affiliation: Department of Clinical Science and Community, Section of Medical Statistics and Biometry, 'GA Maccacaro', University of Milan, Milan, Italy.
authors.forename: Erminio
authors.initials: E
authors.lastname: Bonizzoni
authors.affiliation: Freelance Consultant for phase I clinical trials, Hamburg, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Seiler
authors.affiliation: Medical Affairs Department, Italfarmaco S.p.A., Cinisello Balsamo, Milan, Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Perrone
authors.affiliation: Palliative Care, Pain Therapy and Rehabilitation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.|European Palliative Care Center (PRC), Department of cancer research and molecular medicine NTNU Trondheim, Norway.
authors.forename: Augusto
authors.initials: A
authors.lastname: Caraceni
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D005283:Fentanyl / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D057968:Transdermal Patch; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl
keywords: bilayer matrix; drug delivery; pain; transdermal fentanyl