Characterisation of the Pharmacokinetics of the Fentanyl HCl Patient-Controlled Transdermal System (PCTS)

Abstract

The fentanyl HCl patient-controlled transdermal system (PCTS) is a self-contained, preprogrammed, noninvasive analgesic delivery system for acute pain management. We carried out three studies with the following objectives: study I to evaluate the relationship between fentanyl absorption and the magnitude of current applied to the system; study II to determine dose-proportionality for the fentanyl HCl PCTS (25 and 40 microg); and study III to describe the effects of single- and multiple-day administration on the pharmacokinetics of fentanyl delivered by the PCTS. All studies were open-label, crossover studies with washout periods between treatments. In study I, randomised participants (n = 36) received three of a potential five fentanyl HCl PCTS prototypes, each of which used a different current magnitude, and each of which was evaluated for 24 hours. In study II, participants (n = 40) received fentanyl (25 microg) from the PCTS for 23.33 hours, followed by fentanyl (40 microg) from the PCTS for 23.33 hours. Intravenous (IV) fentanyl (80 microg/h) was administered intermittently over 24 hours as a reference treatment in Studies I and II. In study III, participants (n = 28) received fentanyl (40 microg) from the PCTS for 20 hours, followed by fentanyl (40 microg) from the PCTS for 68 hours. Pharmacokinetic parameters, including maximum serum fentanyl concentration (Cmax), time to Cmax (tmax), area under the serum concentration-time curve (AUC) and terminal half-life (t(1/2)), were determined for each treatment. The amount of fentanyl absorbed from the PCTS was linearly dependent on the magnitude of current applied to the system, with a current of 170 microA resulting in the absorption of 39.5 microg of fentanyl at hour 23. Mixed-effect ANOVA indicated no significant difference (p > 0.1) in the dose-normalised pharmacokinetics of the fentanyl HCl PCTS 25 and 40 microg. No significant difference existed between the corrected AUC(0-5) of the fentanyl HCl PCTS during the single- and multiple-day treatment periods (0.40 and 0.54 microg x h/L, respectively; p = 0.133). The system was well tolerated, with headache and mild application site erythema being the most common treatment-related adverse events. A linear relationship exists between the amount of current applied to the fentanyl HCl PCTS and the amount of fentanyl absorbed. There is dose-proportionality in the pharmacokinetics of the fentanyl HCl PCTS 25 and 40 microg. Multiple-day administration does not affect the pharmacokinetics of the fentanyl HCl PCTS 40 microg. The system was well tolerated, even after repeated application.