Relative bioavailability of different buprenorphine formulations under chronic dosing conditions

Background: Buprenorphine is an approved medication for the treatment of opioid dependence. Three sublingual formulations have been used at various times during its development - a solution containing alcohol, tablets containing buprenorphine alone, and tablets containing buprenorphine plus naloxone. This study compared the relative buprenorphine bioavailability of these different formulations. Methods: Outpatient volunteers (N=10) were maintained for 14 days of daily administration on each formulation; the dose of buprenorphine (8mg) was constant across formulations. Blood samples were collected and tested for buprenorphine and norbuprenorphine concentrations after 7 and 14 days maintenance on each formulation. Serial samples were collected before and for 6h after a daily dose of each formulation. Results: Peak buprenorphine concentrations (C_max) and area under the curve (AUC) for the 6h interval (AUC_0-6) were highest for the solution and lowest for buprenorphine alone tablets; values for combination tablets were more similar to those for solution. Differences between formulations were less pronounced at day 14 than day 7. There was considerable between-subject variability in concentrations produced. Conclusions: These results suggest there may be greater bioavailability of buprenorphine/naloxone versus buprenorphine alone tablets, and that the bioavailability of buprenorphine from the former is very similar to that seen with solution after 2 weeks of stabilization on each formulation.