Bioavailability of Buprenorphine from Crushed and Whole Buprenorphine (Subutex) Tablets

Background: Buprenorphine (Subutex) is the most abused opioid in Finland. In order to curb the abuse potential of this drug, many treatment centers and prisons crush Subutex tablets before administering them to patients. To date, there are no published studies comparing the efficacy and bioavailability of crushed and whole Subutex tablets. Methods: A total of 16 opioid-dependent patients stabilized on 24 mg of buprenorphine were enrolled in a double-blind, double-dummy, randomized cross-over study comparing crushed and whole buprenorphine tablets on a range of pharmacokinetic and pharmacodynamic variables. Buprenorphine tablets (either crushed or whole) and placebo tablets (either crushed or whole) were administered to subjects simultaneously. Buprenorphine and norbuprenorphine serum levels were measured at 30, 60, 90, 120, 180, 240 and 360 min, as well as 24 h, after tablet administration. After 1 week, the experiment was repeated in a cross-over design so that, by the end of the study, each patient had received the active drug (buprenorphine) as both crushed and whole tablets. Results: Pharmacokinetic parameters (mean serum levels, C-max, T-max, AUC) of buprenorphine or norbuprenorphine did not differ significantly between crushed and whole tablets, although serum levels were slightly higher after administration of the crushed tablets. There were also no significant differences in dissolution/absorption time, withdrawal signs or opiate craving. Conclusion: We conclude that crushing Subutex tablets does not significantly alter serum buprenorphine or norbuprenorphine levels or the drug's clinical effect. Our results indicate that crushing Subutex tablets may be used as an alternative method to counter the risk of buprenorphine diversion. Copyright (C) 2010 S. Karger AG, Basel