Sufentanil

Sufentanil Structure

Sufentanil is a strong opioid analgesic currently marketed for IV and epidural anesthesia. There has been published evidence that sufentanil has an analgesic effect, however, its use has been limited due to its short duration of action when delivered intravenously. The pharmaceutical attributes of sufentanil, including lipid solubility and ionization, result in rapid cell membrane penetration and onset of action. In addition, its pharmacokinetic profile when delivered sublingually could potentially avoid the high peak plasma levels and short duration of action of IV administration. In clinical trials, Sufentanil has been shown to be 5- to 10-fold more potent than fentanyl and has the following additional differences that have been observed:

  • No Active Metabolites: Active metabolites can increase the risk of unwanted opioid side effects. Morphine, for example, has the active metabolite morphine-3-glucuronide (M3G) and hydromorphone has the active metabolite hydromorphone-3-glucuronide (H3G), which can accumulate in renally impaired or elderly patients and can contribute to side effects.2-4
  • Rapid Transmucosal Uptake: Sufentanil is highly lipophilic and is readily absorbed through mucosal tissues and distributed throughout the body. This rapid update along with the rapid, 6 minute brain:plasma equiliberation (t1/2ke0), allows sufentanil to exhibit a very rapid onset of analgesia.
  • High Therapeutic Index: In animal studies, sufentanil has one of the highest therapeutic indexes (~27,000) of any commercially available opioid.3 (Therapeutic index, which is an indicator of drug safety, is calculated based on the ratio of the lethal dose to the effective dose). Also, clinical studies have shown that sufentanil provides more effective analgesia with less respiratory depression when compared with equianalgesic doses of fentanyl, morphine, and alfentanil1,5-7. These differences may potentially result in clinically relevant improvements for patients.

These differences are why AcelRx has selected sufentanil for further research into pain management.

References

1: Momeni M, Crucitti M, De KM. Patient-controlled analgesia in the management of postoperative pain. Drugs 2006;66:2321-37.

2: 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.

3: Mather LE. Opioids: a pharmacologist's delight! Clin Exp Pharmacol Physiol 1995;22:833-6.

4: Sear JW, Hand CW, Moore RA, McQuay HJ. Studies on morphine disposition: influence of renal failure on the kinetics of morphine and its metabolites. Br J Anaesth 1989;62:28-32.

5: Ved SA, Dubois M, Carron H, Lea D. Sufentanil and alfentanil pattern of consumption during patient-controlled analgesia: a comparison with morphine. Clin J Pain 1989;5 Suppl 1:S63-S70.

6: Clark NJ, Meuleman T, Liu WS, Zwanikken P, Pace NL, Stanley TH. Comparison of sufentanil-N2O and fentanyl-N2O in patients without cardiac disease undergoing general surgery. Anesthesiology 1987;66:130-5.

7: Bailey PL, Streisand JB, East KA, et al. Differences in magnitude and duration of opioid-induced respiratory depression and analgesia with fentanyl and sufentanil. Anesth Analg 1990;70:8-15.

8: De Castro J. Practical applications and limitations of analgesic anesthesia: a review. Acta Anaesthesiol Belg 1976;27:107-28.

9: Monk JP, Beresford R, Ward A. Sufentanil. A review of its pharmacological properties and therapeutic use. Drugs 1988;36:286-313.

10: Savoia G, Loreto M, Gravino E. Sufentanil: an overview of its use for acute pain management. Minerva Anestesiol 2001;67:206-16.

11: Brusset A, Levron JC, Olivier P, et al. Comparative pharmacokinetic study of fentanyl and sufentanil after single high-bolus doses. Clin Drug Invest 1999;18:377-89.

12: Stoeckel H, Schuttler J, Magnussen H, Hengstmann JH. Plasma fentanyl concentrations and the occurrence of respiratory depression in volunteers. Br J Anaesth 1982;54:1087-95.

13: Becker LD, Paulson BA, Miller RD, Severinghaus JW, Eger EI. Biphasic respiratory depression after fentanyldroperidol or fentanyl alone used to supplement nitrous oxide anesthesia. Anesthesiology 1976;44:291-6.

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