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Pharmacokinetics of Sublingual Sufentanil Tablets and Efficacy and Safety in the Management of Postoperative Pain

Minkowitz, Harold S. MD*; Singla, Neil K. MD; Evashenk, Mark A. BS; Hwang, Stephen S. PhD; Chiang, Yu-Kun PhD; Hamel, Lawrence G. BS; Palmer, Pamela P. MD, PhD

Regional Anesthesia & Pain Medicine: March/April 2013 - Volume 38 - Issue 2 - p 131–139
doi: 10.1097/AAP.0b013e3182791157
Original Articles

Background and Objectives: A sublingual sufentanil tablet is being developed as a potential alternative to intravenous (IV) opioids for the management of postoperative pain. The objective of these studies was to evaluate the pharmacokinetics, efficacy, and safety of sublingual sufentanil tablets for postoperative pain management.

Methods: The pharmacokinetics of sublingual sufentanil 10 and 80 µg were compared with IV sufentanil in 12 subjects in a phase 1 study. The safety and efficacy of sublingual sufentanil (5–15 µg) were evaluated in double-blind, randomized, placebo-controlled phase 2 studies in patients undergoing knee replacement surgery (n = 101) or open abdominal (ABD) surgery (n = 94). The primary efficacy measurement was the summed pain intensity difference compared with baseline over 12 hours (SPID-12).

Results: Sublingual sufentanil pharmacokinetics were dose proportional following single doses of 10 and 80 µg. Plasma half-time (time from peak plasma concentration to 50% of peak concentration) was 80 to 90 minutes for sublingual sufentanil compared with 15 minutes or less for IV sufentanil. In the phase 2 studies, greater SPID-12 scores (ie, lower pain intensity) compared with placebo were observed for sublingual sufentanil 15 µg in the knee replacement study (P < 0.05) and for 10 and 15 µg in the ABD study (P < 0.01). All doses of sublingual sufentanil were well tolerated, and the incidence of adverse events was similar between the sublingual sufentanil and placebo groups.

Conclusions: Sufentanil formulated as a sublingual solid dosage form provides a duration of action that allows effective analgesia for postoperative patients in a medically supervised setting.

From the *Memorial Hermann Memorial City Medical Center, Houston, TX; and †Lotus Clinical Research, Pasadena, CA; and ‡AcelRx Pharmaceuticals, Redwood City, CA.

Accepted for publication October 11, 2012.

Address correspondence to: Pamela P. Palmer, MD, PhD, AcelRx Pharmaceuticals, 351 Galveston Dr, Redwood City, CA 94063 (e-mail: ppalmer@acelrx.com).

Joseph M. Neal, MD, served as editor in-chief for this article.

AcelRx Pharmaceuticals, Redwood City, California, provided the sole funding of these phase 1 and phase 2 studies.

Some of these data were presented at the American Society of Anesthesiologists Annual Meeting 2009 in New Orleans, LA; the American Society of Regional Anesthesia and Pain Management Spring Meeting 2010 in Toronto, Ontario, Canada; and the American Pain Society Annual Meeting 2011 in Austin, TX.

Drs. Minkowitz and Singla received research funding to conduct the phase 2 clinical studies. Drs. Hwang and Chiang were paid consultants in the area of pharmacokinetics and statistical design and analysis, respectively. Mr. Hamel, Mr. Evashenk, and Dr. Palmer are employees and stock owners of AcelRx Pharmaceuticals and were responsible for the design and conduct of the studies and writing of the manuscript.

Editorial assistance was provided by Jacqueline Wu, PhD (Castle Peak Medical Writing, Tucson, Arizona) on behalf of AcelRx Pharmaceuticals, Inc.

©2013 American Society of Regional Anesthesia and Pain Medicine