Sufentanil
Sufentanil is an opioid analgesic currently marketed for IV and epidural anesthesia and analgesia; however, its postoperative use has been limited due to its short duration of action when delivered intravenously.1
The pharmaceutical attributes of sufentanil, including lipid solubility and degree of non-ionization, result in rapid cell membrane penetration allowing entry into the central nervous system (CNS).2 In addition, its pharmacokinetic profile when delivered sublingually could potentially avoid the high peak plasma levels and short duration of action observed with IV administration.3 Sufentanil has been shown to be 5- to 10-fold more potent than fentanyl4. The following additional differences to other opioids have been observed:
No Active Metabolites: Active metabolites can increase the risk of delayed opioid side effects. Morphine, for example, has the active metabolite morphine-6-glucuronide (M6G) and M3G and hydromorphone has the active metabolite hydromorphone-6-glucuronide (H6G) and H3G, which can accumulate in renally impaired or elderly patients.5-7
Rapid Transmucosal Uptake: Sufentanil is highly lipophilic and is readily absorbed through mucosal tissues8 and distributed throughout the body. The short 6-minute brain:plasma equilibration half-life (t1/2ke0) of sufentanil demonstrates its ease of penetrating into the CNS.9
High Therapeutic Index: In animal studies, sufentanil has one of the highest therapeutic indexes (~27,000) of any commercially available opioid.10 The therapeutic index is the ratio of the lethal dose to the effective dose of a drug. These differences may potentially result in clinically relevant improvements for patients.
AcelRx's proprietary, noninvasive sublingual formulation technology efficiently delivers highly lipophilic drugs with consistent pharmacokinetic profiles. These sublingual dosage forms are designed to minimize the natural saliva response, thereby potentially reducing the amount of swallowed drug that results from typical oral transmucosal products. Drug absorbed from the gastrointestinal (GI) tract can potentially lead to more erratic and delayed timing to peak plasma levels compared to transmucosal absorbtion.10,11
Sufentanil Sublingual Mechanism of Action
