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TRIAL - SAFETY OF BUPRENORPHINE: CEILING FOR CARDIO-RESPIRATORY EFFECTS AT HIGH IV DOSES
CONDUCTED BY - A. Umbricht, M. A. Huestis, E. J Cone, and K. L. Preston
CONDUCTED AT - NIDA Intramural Research Program, Baltimore, MD
Buprenorphine is a partial opioid agonist and an antagonist that is used for the treatment of opioid dependence. The safety of sublingual buprenorphine in experienced opioid users without physical dependence has been reported at doses up to 32 mg. 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. In this dose-ranging study, the safety of buprenorphine was tested in a single-blind, double-dummy design, according to the following schedule: SL:12 mg/placebo; IV bolus: 0, 2, 4, 8, 12, and 16 mg, in sessions separated by at least 72 hours. SL doses (or placebo) were held in the mouth for 5 min, followed immediately by an IV injection (1 minute) in 6 experienced opioid users without opioid dependence. (Sixteen mg IV buprenorphine is equivalent to 4 - 11 times Fentanyl doses used to induce apnea during opioid anesthesia.) Vital signs and oxygen saturation were monitored continuously for 3 hours while the subject remained in a sitting position performing computer tasks and later on a residential unit. Analysis of the Area Under the Curve showed a statistically significant increase from baseline in Systolic Blood Pressure for the 8 mg IV dose compared to the placebo condition (+ 13.5 mm Hg). There were no other statistically significant changes in blood pressure, heart rate or oxygen saturation among the 7 drug conditions. The mean (± SD) maximum decrease in 02 saturation from baseline was greatest for the 8 mg IV dose: -7.3 (±4.3). The main side effects were sedation, mild irritability, nausea, and itching. One subject's participation was discontinued after the 12 mg IV dose because of severe nausea, which persisted for 24 hours. Subjects remained responsive to low voice and computer prompts for tasks performances. Buprenorphine appears to have a ceiling for cardio-respiratory effects and a high safety margin when administered by the IV route in the absence of other drugs.
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