|Titre :||Effects of buprenorphine/naloxone in opioid-dependent humans (2001)|
|Auteurs :||K. B. STOLLER ; G. E. BIGELOW ; S. L. WALSH ; E. C. STRAIN|
|Type de document :||Article : Périodique|
|Dans :||Psychopharmacology (Vol.154, n°3, March 2001)|
|Article en page(s) :||230-242|
|Discipline :||TRA (Traitement et prise en charge / Treatment and care)|
Thésaurus TOXIBASETRAITEMENT DE MAINTENANCE ; BUPRENORPHINE ; NALOXONE ; OPIOIDES ; ETUDE CLINIQUE ; ANTAGONISTE ; HEROINE ; TEST ; PHYSIOLOGIE
Rationale : Buprenorphine is a partial mu opioid agonist under development as a sublingual (SL) medication for opioid dependence treatment in the United States. Because buprenorphine may be abused, tablets combining buprenorphine with naloxone in a 4:1 ratio have been developed to reduce that risk. Low doses of injected buprenorphine/naloxone have been tested in opioid-dependent subjects, but higher doses (more than 2 mg of either medication) and direct comparisons to SL buprenorphine/naloxone have not been examined.
Objectives : To assess and compare the effects of intramuscular (IM) versus SL buprenorphine/naloxone in opioid-dependent volunteers.
Methods : Opioid-dependent volunteers were maintained on 40 mg per day of oral hydromorphone while on a residential research ward. After safety testing in two pilot subjects, participants (n=8) were tested with both IM and SL buprenorphine/naloxone (1/0.25, 2/0.5, 4/1, 8/2, 16/4 mg); IM hydromorphone (10 mg) and naloxone (0.25 mg); both IM and SL buprenorphine alone (8 mg); and placebo. Test sessions were twice per week; dosing was double-blind.
Results : Intramuscular buprenorphine/naloxone produced dose-related increases on indices of opioid antagonist effects. Effects were consistent with naloxone-precipitated withdrawal, and were short-lived. As withdrawal effects dissipated, euphoric opioid agonist effects from buprenorphine did not appear. Sublingual buprenorphine/naloxone produced neither opioid agonist nor antagonist effects.
Conclusions : Intramuscular injection of buprenorphine/naloxone precipitates withdrawal in opioid dependent persons; therefore, the combination has a low abuse potential by the injection route in this population. Sublingual buprenorphine/naloxone by tablet is well tolerated in opioid dependent subjects, and shows neither adverse effects (i.e., precipitated withdrawal) nor a high abuse potential (i.e., opioid agonist effects).
|Domaine :||Drogues illicites / Illicit drugs|
|Affiliation :||Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA|