Following DURAGESIC® application, the skin under the system absorbs fentanyl, and a depot of fentanyl concentrates in the upper skin layers. Fentanyl then becomes available to the systemic circulation. Serum fentanyl concentrations increase gradually following initial DURAGESIC® application, generally leveling off between 12 and 24 hours and remaining relatively constant, with some fluctuation, for the remainder of the 72-hour application period. Peak serum concentrations of fentanyl generally occurred between 24 and 72 hours after initial application (see Table A). Serum fentanyl concentrations achieved are proportional to the DURAGESIC® delivery rate. With continuous use, serum fentanyl concentrations continue to rise for the first few system applications. After several sequential 72-hour applications, patients reach and maintain a steady state serum concentration that is determined by individual variation in skin permeability and body clearance of fentanyl (see graph and Table B).
