Bioequivalence and safety of a novel fentanyl transdermal matrix system compared with a transdermal reservoir system

Abstract

Fentanyl is a potent synthetic opioid used for the management of chronic pain. A newer transdermal matrix system was developed and compared with a reservoir system used in the United States. An open-label, single-center, randomized, two-period crossover study was conducted to evaluate the bioequivalence of the transdermal matrix system to the transdermal reservoir system. Seventy-four subjects completed treatment with both the reservoir system (100 microg/h) and the matrix system (100 microg/h), each applied for 72 hours. After application of the first system, subjects completed a 9-day washout and then crossed over to receive the other system for another 72 hours. Blood samples for the determination of serum fentanyl concentrations were taken in each treatment period for up to 120 hours following application. The ratios of geometric means for maximum fentanyl concentration (Cmax) and area under the concentration-time curve (AUClast, and AUCinfinity) were 106 percent, 110 percent, and 110 percent, respectively. The 90% confidence intervals for the ratios of the geometric means were contained within the bioequivalence criteria of 80-125 percent. The matrix system adhered well to skin. Systemic and topical safety profiles were comparable between treatments. The transdermal fentanyl matrix system adhered well, was well tolerated, and produced systemic exposures of fentanyl that were bioequivalent to the reservoir system.