This study assessed the absolute and relative bioavailabilities and transmucosal and gastrointestinal absorbency of fentanyl buccal tablet (FBT) and oral transmucosal fentanyl citrate (OTFC). In a randomized crossover design, 26 healthy subjects received FBT 400 microg (transmucosal), FBT 800 microg (oral), OTFC 800 microg (transmucosal), and fentanyl 400 microg (intravenous). The transmucosal FBT had the highest absolute bioavailability (0.65) compared with the oral FBT (0.31) or transmucosal OTFC (0.47). More fentanyl was absorbed transmucosally from FBT than OTFC (48% vs 22%). Median t(max) values were shorter following the transmucosal FBT (47 minutes) than the oral FBT (90 minutes) or the transmucosal OTFC (91 minutes). Transmucosal administration of FBT compared with dose-normalized OTFC resulted in higher total systemic fentanyl exposure, higher early systemic exposure, and higher C(max). The rate and extent of fentanyl absorption were greater following administration of FBT compared to OTFC. An approximately 30% smaller dose of FBT achieved systemic exposures comparable to OTFC.