Effects of buprenorphine and naloxone in morphine-stabilized opioid addicts.
The present study, conducted as part of the development of a buprenorphine/naloxone combination product, was designed to evaluate the individual and combined effects of intravenously administered buprenorphine and naloxone. This in-patient trial used a randomized, double-blind, crossover design. Ten opioid-dependent male subjects were stabilized and maintained on morphine, 15 mg given intramuscularly four times daily. Then, at 48- to 72-h intervals, subjects received one of the following by intravenous injection: (1) placebo, (2) morphine 15 mg, (3) buprenorphine 2 mg, (4) buprenorphine 2 mg/naloxone 0.5 mg, and (5) naloxone 0.5 mg. Both naloxone and buprenorphine/naloxone produced significant (P < 0.005) opioid withdrawal effects compared to placebo as assessed with the CINA scale, an instrument which utilizes subject- and observer-reported, as well as physiological parameters. The combination of buprenorphine with naloxone in a 4:1 ratio produced opioid antagonist-like effects which should limit its potential for intravenous abuse by opioid addicts.
Fudala
P J
PJ
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, USA.
Yu
E
E
Macfadden
W
W
Boardman
C
C
Chiang
C N
CN
D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D016739:Behavior, Addictive / Q000209:etiology; D002047:Buprenorphine / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use; D009270:Naloxone / Q000008:administration & dosage / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D009294:Narcotics / Q000008:administration & dosage / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D013997:Time Factors; D014728:Veterans
D004338:Drug Combinations; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D002047:Buprenorphine; D009020:Morphine