An injection depot formulation of buprenorphine: extended bio-delivery and effects

Buprenorphine is an effective medication for treatment of opioid dependence. An injectable depot formulation of buprenorphine has been developed using biodegradable polymer microcapsule technology. This formulation may offer effective treatment of opioid dependence and enhance treatment delivery while minimizing risks of patient non-adherence or illicit diversion of the medication. This report provides a characterization of the bio-delivery of this injectable depot in humans and of the relationship of drug blood levels to pharmacodynamic indices.

The data are from two studies in which 11 opioid-dependent volunteers each received a single depot injection containing 58 mg of buprenorphine, and include previously unreported detailed plasma concentration data over a 6-week time-course following depot administration and examination of their relationship to pharmacodynamic indices.

Mean plasma buprenorphine increased gradually following depot administration, peaked at 2-3 days with a mean concentration of 1.25 ng/ml and then decreased gradually, approaching undetectable levels (< 0.10 ng/mL) by 6 weeks. There was substantial between-subject consistency in several aspects of buprenorphine bio-delivery, including time to first detectable blood level (4 hours), peak blood level (2 days) and undetectable blood level (6-6.5 weeks). In contrast, there was marked between-subject variability in the magnitude of peak buprenorphine concentrations, ranging from 0.17 to 3.47 ng/ml. Extent of opioid blockade was tested by weekly opioid challenges with 3 mg subcutaneous hydromorphone; subjective response and pupillary constriction were related inversely to both buprenorphine and norbuprenorphine plasma concentrations (r=0.84-0.95).

The data document that this depot formulation provides effective buprenorphine delivery for several weeks and that effects persist even at fairly low buprenorphine plasma concentrations. Suggestions are offered for further research needed to develop this formulation for clinical use as a detoxification and/or maintenance pharmacotherapy for opioid dependence.