Proposed are studies of the duration of buprenorphine blockade of the effects of challenge doses of hydromorphone. These studies build on the investigator's published finding that blockade of exogenous hydromorphone effects by buprenorphine appears to last for at least three days. The initial proposed studies will involve sequential, randomized, single- blind discontinuation of active buprenorphine for 1, 3, 5, or 7 days in buprenorphine-dependent patients. At the end of these discontinuation periods, addicts will be challenged with intramuscular hydronorphone to assess the extent of blockade present. A proposed follow-up study extends the study of duration of buprenorphine blockade to blockade by single doses of buprenorphine in subjects who are not opiate dependent. Plasma buprenorphine levels will be collected in each of the above studies 1, 6, and 24 hours after the last buprenorphine dose, and immediately before the hydromorphone challenges. Across-subject comparisons will allow us to determine whether inter-individual differences have a pharmacokinetic basis. The studies will define the relationship, if there is any, between (drug exposure) plasma levels and duration of buprenorphine's actions. The proposed research might suggest innovative buprenorphine dosing schedules. A careful description concomitantly of the clinical phenomena of buprenorphine blockade, withdrawal, and plasma levels is proposed.
Showing the most recent 10 out of 39 publications
