FENTANYL

Fentanyl is available in a variety of preparations for parenteral, transdermal and transmucosal (including buccal) administration. Because of high firstpass metabolism (~70%) it is not given orally. It is approximately 80–100 times more potent than morphine in the acute seing, although it is approximately 30–40 times as potent when given chronically (e.g. slowrelease transdermal patches). With transdermal administration, the patch and underlying dermis act as a reservoir, and plasma concentration does not reach steady state until approximately 15h after initial application. Plasma concentration also declines slowly after removal (t1/2 ~15–20 h).
Fentanyl is very lipophilic, with a relatively short duration of action. There are several new buccal/transmucosal preparations developed for rapid-onset breakthrough pain. These aim to have a very rapid onset in approximately 10min, although this may not be the case in clinical practice. Fentanyl has a large VD with rapid peripheral tissue uptake, limiting initial hepatic metabolism. This may result in significant variability in plasma concentrations and secondary plasma peaks. It binds to αl-acid glycoprotein and albumin; 40% of the protein-bound fraction is taken up by erythrocytes. The lungs may be important in exerting a first-pass effect on fentanyl (up to 75% of the dose), thus buffering the plasma from high peak drug concentrations.