Improving the oral bioavailability of buprenorphine: an in-vivo proof of concept.

Objectives: The aim of this study was to improve the oral bioavailability of buprenorphine by inhibiting presystemic metabolism via the oral co-administration of 'Generally Recognized as Safe' compounds, thus providing an orally administered drug product with less variability and comparable or higher exposure compared with the sublingual route.

Methods: The present studies were performed in Sprague Dawley rats following either intravenous or oral administration of buprenorphine/naloxone and oral co-administration of 'Generally Recognized as Safe' compounds referred to as 'adjuvants'. Plasma samples were collected up to 22 h postdosing followed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analysis.

Key Findings: The adjuvants increased C (21 ± 16 ng/ml vs 75 ± 33 ng/ml; 3.6-fold) and AUC (10.6 ± 8.11 μg min/ml vs 22.9 ± 11.7 μg min/ml; 2.2-fold) values of buprenorphine (control vs adjuvant-treated, respectively). The absolute oral bioavailability of buprenorphine doubled (from 1.24% to 2.68%) in the presence of the adjuvants.

Conclusions: One may suggest that the adjuvant treatment most likely inhibited the presystemic metabolic enzymes, thus decreasing the intestinal 'first-pass effect' on buprenorphine. Additional studies are now required to further explore the concept of inhibiting presystemic metabolism of buprenorphine by adjuvants to potentially increase the oral bioavailability of buprenorphine.