title: Bioavailability of a novel midazolam gel after intranasal administration in dogs.
abstract: OBJECTIVE
  To compare the pharmacokinetics of a novel bioadhesive gel formulation of midazolam after intranasal (IN) administration with that of midazolam solution after IN, IV, and rectal administration to dogs.
  
  
  METHODS
  10 (5 males and 5 females) healthy adult Beagles.
  
  
  METHODS
  Dogs were assigned to 4 treatment groups for a crossover study design. Initially, midazolam solution (5 mg/mL) was administered (0.2 mg/kg) IV to group 1, rectally to group 2, and IN to group 3; a 0.4% hydroxypropyl methylcellulose midazolam gel formulation (50 mg/mL) was administered (0.2 mg/kg, IN) to group 4. Each dog received all 4 treatments; there was a 7-day washout period between subsequent treatments. Blood samples were collected before and after midazolam administration. Plasma concentration of midazolam was determined by use of high-performance liquid chromatography.
  
  
  RESULTS
  The peak plasma concentration after IN administration of the gel formulation was significantly higher than that after IN and rectal administration of the solution. Mean ± SD time to peak concentration was 11.70 ± 2.63 minutes (gel IN), 17.50 ± 2.64 minutes (solution IN), and 39 ± 14.49 minutes (solution rectally). Mean bioavailability of midazolam was 70.4% (gel IN), 52.0% (solution IN), and 49.0% (solution rectally). Bioavailability after IN administration of the gel formulation was significantly higher than that after IN and rectal administration of the solution.
  
  
  CONCLUSIONS
  IN administration of midazolam gel was superior to both IN and rectal administration of midazolam solution with respect to peak plasma concentration and bioavailability.
authors.affiliation: Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. boiadeiro66@hotmail.com
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Eagleson
authors.forename: Simon R
authors.initials: SR
authors.lastname: Platt
authors.forename: Deborah L Elder
authors.initials: DL
authors.lastname: Strong
authors.forename: Marc
authors.initials: M
authors.lastname: Kent
authors.forename: Anne C
authors.initials: AC
authors.lastname: Freeman
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nghiem
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.forename: Catherine A
authors.initials: CA
authors.lastname: White
mesh_terms: D000281:Administration, Intranasal; D000285:Administration, Rectal; D000818:Animals; D001682:Biological Availability; D018592:Cross-Over Studies; D004285:Dogs; D005260:Female; D005782:Gels; D006207:Half-Life; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008874:Midazolam / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D012996:Solutions
chemical_list: D005782:Gels; D006993:Hypnotics and Sedatives; D012996:Solutions; D008874:Midazolam