title: Evaluation of the clearance of a sublingual buprenorphine spray in the beagle dog using gamma scintigraphy.
abstract: OBJECTIVE
  The aim of this study was to evaluate clearance from the buccal cavity and pharmacokinetic profiles of a sublingual spray formulation in the dog, to assist in interpretation of future pharmacokinetic studies.
  
  
  METHODS
  Radiolabelled buprenorphine in a spray formulation (400 microg/100 microl in 30% ethanol) was administered sublingually to four beagle dogs, and the residence in the oral cavity was determined using gamma scintigraphy. Pharmacokinetic sampling was performed to facilitate correlation of location of dose with significant pharmacokinetic events.
  
  
  RESULTS
  Scintigraphic imaging revealed that clearance of the formulation from the oral cavity was rapid, with a mean T 50% clearance of 0.86 +/- 0.46 min, and T 80% clearance of 2.75 +/- 1.52 min. In comparison, absorption of buprenorphine was relatively slow, with a T max of 0.56 +/- 0.13 h. Good buccal absorption despite short residence time can be explained by lipophilicity of buprenorphine enabling rapid sequestration into the oral mucosa, prior to diffusion and absorption directly into systemic circulation.
  
  
  CONCLUSIONS
  This study demonstrated rapid clearance of a sublingual solution from the canine oral cavity, with T 50% similar to results previously reported in man, providing initial confidence in using a conscious dog model to achieve representative residence times for a sublingual solution.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR, UK. fiona.mcinnes@strath.ac.uk
authors.forename: Fiona
authors.initials: F
authors.lastname: McInnes
authors.forename: Nicola
authors.initials: N
authors.lastname: Clear
authors.forename: Gerry
authors.initials: G
authors.lastname: James
authors.forename: Howard N E
authors.initials: HN
authors.lastname: Stevens
authors.forename: Unai
authors.initials: U
authors.lastname: Vivanco
authors.forename: Michael
authors.initials: M
authors.lastname: Humphrey
mesh_terms: D000042:Absorption; D000286:Administration, Sublingual; D000336:Aerosols; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D002047:Buprenorphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs; D015902:Gamma Cameras; D008297:Male; D009055:Mouth / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009061:Mouth Mucosa / Q000378:metabolism; D011877:Radionuclide Imaging; D015203:Reproducibility of Results
chemical_list: D000336:Aerosols; D000701:Analgesics, Opioid; D002047:Buprenorphine