|SOFT - TIAFT 1998||Scientific Session 1||Wednesday October 7, 1998|
|SAFETY OF BUPRENORPHINE: CEILING FOR CARDIO-RESPIRATORY AND SUBJECTIVE EFFECTS AT HIGH IV DOSES|
|Marilyn A. Huestis, Annie Umbricht, Kenzie L. Preston, and Edward J. Cone|
NIDA Intramural Research Program, 5500 Nathan Shock Dr., Baltimore, MD 21224.
|Buprenorphine (BUP), a partial m agonist and k antagonist, is under development for treatment of opioid dependence. The present study was conducted to test the safety and abuse potential of intravenous (IV) BUP in the range of doses used for maintenance treatment. Concerns have been raised about the potential acute health risk of buprenorphine if diverted and used by the IV route at doses equivalent to those used for maintenance. Subjective effects of BUP SL (12 mg) and IV/SL placebo (in random order) and BUP IV (2, 4, 8, 12, and 16 mg in increasing dose order) were evaluated in separate sessions in this single-blind, double-dummy study. Data were collected from 6 non-dependent male opioid abusers. Safety parameters included continuous monitoring of vital signs and oxygen saturation for 3 h after drug administration and additional collections over the next 72 h. Subjective measures included visual analog scales of global drug effects, ARCI subscales, and adjective rating scales. An increase in Systolic Blood Pressure for the 8 mg IV dose (+ 13.5 mm Hg) as compared to placebo was the only statistically significant change in blood pressure, heart rate or oxygen saturation among the 7 drug conditions. The mean maximum decrease in 02 saturation was greatest for the 8 mg IV dose (-7.3%). The main side effects were sedation, mild irritability, nausea, and itching. One subject did not receive the 16 mg IV dose because of severe nausea, which persisted for 24 hours (28 to 72 hr on some measures). Subjective measures included visual analog scales of global drug effects, ARCI subscales, and adjective rating scales. All active BUP conditions produced increases in positive subjective measures compared to placebo, including high, drug effect, good effects, drug liking, opioid agonist adjective rating scale, and MBG scale of the ARCI. Peak effects occurred 1 to 1.5 h after IV doses and 3 to 6 h after SL BUP. Duration of action was 24 hours or longer. Effects did not increase in an orderly dose-related manner; on many measures, the magnitude of effect was not different among all active doses. The effects of 16 mg IV tended to be less than those of 12 mg IV and varied in comparison to other active doses. Buprenorphine appears to have a ceiling for cardio-respiratory and subjective effects and a high safety margin when administered by the IV route in the absence of other drugs.|