Transdermal fentanyl: clinical pharmacology

The transdermal therapeutic system (TTS) fentanyl has been designed for rate-controlled drug delivery. It provides a convenient regimen for the use of a drug previously limited by a short duration of action and a noninvasive parenteral route for a drug that is unsuitable for oral administration. TTS fentanyl has been developed to provide continuous controlled systemic delivery of fentanyl base for 72 hr. It is a rectangular, transparent unit composed of a protective peel strip and four functional layers. The amount of fentanyl released from each system (25 micrograms/hr per 10 cm2) is proportional to the surface area. So far, four patch sizes are available (10-40 cm2). When the system is applied, a fentanyl depot concentrates in the upper skin layers. Fentanyl plasma concentrations are not measurable until 2 hr after application, and it takes 8-16 hr latency until full clinical fentanyl effects are observed. Steady-state serum concentrations are obtained after several sequential 72-hr applications, and these are maintained for as long as a system is applied. Following removal, serum fentanyl concentrations decline gradually and fall about 50% in approximately 16 hr. This prolonged apparent elimination half-life occurs because fentanyl continues to be absorbed from the skin. Transdermal fentanyl transport is essentially the same between the chest, abdomen, and thigh. The skin-permeability constant is about 0.0125 mL/hr/cm2, much lower than the regional blood supply to a chest-skin area. Because of potential permeability variations among individuals, a special rate-controlling membrane in the system provides additional control of drug release.(ABSTRACT TRUNCATED AT 250 WORDS)