Pharmacokinetic study between a bilayer matrix fentalyl patch and a monolayer matrix fentanyl patch: single dose administration in healthy volunteers

Ernesto Zecca, Andrea Manzoni, Fabio Centurioni, Alberto Farina, Erminio Bonizzoni, Dan Seiler, Tania Perrone, Augusto Caraceni

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aims 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 Cmax 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 Cmax ratio (114.4% [105.8, 123.8%] were well included in the acceptance range and the Cmax 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).

Original languageEnglish
Pages (from-to)110-115
Number of pages6
JournalBritish Journal of Clinical Pharmacology
Volume80
Issue number1
DOIs
Publication statusPublished - Jul 1 2015

Fingerprint

Fentanyl
Healthy Volunteers
Pharmacokinetics
Area Under Curve
Confidence Intervals
Device Removal
Therapeutic Equivalency
Skin
Pharmaceutical Preparations
Cross-Over Studies
Opioid Analgesics
Biological Availability
Tissue Donors
Clinical Trials
Safety

Keywords

  • bilayer matrix
  • drug delivery
  • pain
  • transdermal fentanyl

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Pharmacokinetic study between a bilayer matrix fentalyl patch and a monolayer matrix fentanyl patch : single dose administration in healthy volunteers. / Zecca, Ernesto; Manzoni, Andrea; Centurioni, Fabio; Farina, Alberto; Bonizzoni, Erminio; Seiler, Dan; Perrone, Tania; Caraceni, Augusto.

In: British Journal of Clinical Pharmacology, Vol. 80, No. 1, 01.07.2015, p. 110-115.

Research output: Contribution to journalArticle

Zecca, Ernesto ; Manzoni, Andrea ; Centurioni, Fabio ; Farina, Alberto ; Bonizzoni, Erminio ; Seiler, Dan ; Perrone, Tania ; Caraceni, Augusto. / Pharmacokinetic study between a bilayer matrix fentalyl patch and a monolayer matrix fentanyl patch : single dose administration in healthy volunteers. In: British Journal of Clinical Pharmacology. 2015 ; Vol. 80, No. 1. pp. 110-115.
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AU - Farina, Alberto

AU - Bonizzoni, Erminio

AU - Seiler, Dan

AU - Perrone, Tania

AU - Caraceni, Augusto

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N2 - Aims 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 Cmax 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 Cmax ratio (114.4% [105.8, 123.8%] were well included in the acceptance range and the Cmax 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).

AB - Aims 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 Cmax 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 Cmax ratio (114.4% [105.8, 123.8%] were well included in the acceptance range and the Cmax 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).

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