Sublingual 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 and 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 and can contribute to side effects.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, non-invasive 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

 

  1. Fries, D.S. (2010). Opioid Analgesics. In Lemke, T.L. & Williams, D.A. (Eds.), Foye's Principles of Medicinal Chemistry (pp. 672). Wolters Kluwer Health, 2008
  2. Part III: Opioids, an Integrative Part in Perioperative Medicine. In Freye, E. (Ed.), Opioids in Medicine: a Comprehensive Review on the Mode of Action and the Use of Analgesics in Different Clinical Pain States (pp. 207-8). Springer Science & Business Media, Mar 12, 2008
  3. Minkowitz, H.S. et al. Pharmacokinetics of sublingual sufentanil tablets and efficacy and safety in the management of postoperative pain. Reg Anesth Pain Med. 2013 Mar-Apr;38(2):131-9
  4. Deshpande, C.M., Mohite, S.N. and Kamdi, P. Sufentanil Vs Fentanyl for Fast-Track Cardiac Anaesthesia. Indian J Anaesth. 2009 Aug; 53(4): 455–462
  5. Ratka A, Wittwer E, Baker L, Kern S. Pharmacokinetics of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in healthy older men and women. Am J Pain Manag 2004;14:45-55
  6. Mather L.E. Opioids: a Pharmacologist's Delight! Clin Exp Pharmacol Physiol 1995;22:833-6
  7. Sear J.W., et al. Studies on Morphine Disposition: Influence of Renal Failure on the Kinetics of Morphine and its Metabolites. Br J Anaesth 1989;62:28-32
  8. Reisfield, G.M., & Wilson, G.R. Rational Use of Sublingual Opioids in Palliative Medicine. J Palliat Med. 2007 Apr;10(2):465-75
  9. Shafer SL, Varvel JR: Pharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology 1991; 74:53
  10. Mather LE. Opioids: a pharmacologist's delight!  Clin Exp Pharmacol Physiol 1995; 22:833-6.
  11. The Joint Commission on Accreditation of Healthcare Organizations; the National Pharmaceutical Council. Pain: Current Understanding of Assessment, Management, and Treatments. 2005