title: Improving the oral bioavailability of buprenorphine: an in-vivo proof of concept.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  The adjuvants increased Cmax(21 ± 16 ng/ml vs 75 ± 33 ng/ml; 3.6-fold) and AUC(0-22 h)(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.
authors: Department of Pharmaceutics, VCU School of Pharmacy, Richmond, VA, USA.
authors: Anand
authors: A
authors: Joshi
authors: Department of Pharmaceutics, VCU School of Pharmacy, Richmond, VA, USA.
authors: Matthew
authors: M
authors: Halquist
authors: Global Research & Development, Indivior Inc., Richmond, VA, USA.
authors: Zacharoula
authors: Z
authors: Konsoula
authors: Global Research & Development, Indivior Inc., Richmond, VA, USA.
authors: Yongzhen
authors: Y
authors: Liu
authors: Global Research & Development, Indivior Inc., Richmond, VA, USA.
authors: J P
authors: JP
authors: Jones
authors: Global Research & Development, Indivior Inc., Richmond, VA, USA.
authors: Christian
authors: C
authors: Heidbreder
authors: Department of Pharmaceutics, VCU School of Pharmacy, Richmond, VA, USA.
authors: Phillip M
authors: http://orcid.org/0000-0001-9861-1018
authors: PM
authors: Gerk
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002047:Buprenorphine / Q000097:blood / Q000493:pharmacokinetics*; D002460:Cell Line; D002853:Chromatography, Liquid; D006801:Humans; D008658:Inactivation, Metabolic / Q000187:drug effects; D007408:Intestinal Absorption / Q000187:drug effects*; D019684:Magnoliopsida / Q000737:chemistry*; D008297:Male; D009270:Naloxone / Q000097:blood / Q000493:pharmacokinetics; D010936:Plant Extracts / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D000277:Adjuvants, Pharmaceutic; D010936:Plant Extracts; D009270:Naloxone; D002047:Buprenorphine
keywords: buprenorphine; liquid chromatography coupled to tandem mass spectrometry; oral bioavailability; presystemic metabolism