Results: Bioavailability of a single sublingual tablet was 52%, decreasing to 35% with repeat dosing. Ketoconazole (CYP3A4 inhibitor) increased maximum plasma concentration 19% and increased the area under the curve 77%. After a single 30-µg dose, plasma concentrations reached the published sufentanil analgesic threshold (24 pg/ml) within 30 min, peaked at 1 h, and then decreased below therapeutic concentrations by ~3 h. With hourly administration, plasma concentrations plateaued by the fifth dose. Time for concentrations to decrease 50% from maximal values was similar after 1 dose (2.5 ± 0.85 h) and 12 doses (2.5 ± 0.72 h). Clearance increased with weight, decreased with age, and was not affected by renal or hepatic impairment.
Conclusions: The time course of a single 30-µg dose was consistent with onset of analgesia and redosing frequency observed in clinical trials. Sublingual sufentanil tablets provide the opportunity to noninvasively and rapidly treat moderate-to-severe pain in a monitored setting.
Oral transmucosal delivery offers a noninvasive route for rapid absorption of lipophilic opioids
Available transmucosal fentanyl or buprenorphine products often contain large doses of these opioids and are not suitable for acute use in opioid-naive patients
With sublingual administration of a newly developed 30-μg sufentanil tablet, the time to maximum plasma concentration was approximately 1 h, but the analgesic threshold was typically reached at or before 30 min, which is consistent with the onset of analgesia observed in clinical trials of the 30-μg product
The time for the plasma concentrations to decrease below the analgesic threshold after a single 30-μg dose was approximately 3 h, which is consistent with the duration of analgesia in those published clinical trials