Bioavailability of a novel midazolam gel after intranasal administration in dogs

• Published in: American journal of veterinary research Vol. 73; no. 4; pp. 539 - 545
• Main Authors: Eagleson, Joseph S, Platt, Simon R, Strong, Deborah L. Elder, Kent, Marc, Freeman, Anne C, Nghiem, Peter P, Zheng, Bo, White, Catherine A
• Format: Journal Article
• Language: English
• Published: United States 01.04.2012
• Subjects: Administration, Intranasal; Administration, Rectal; adults; Animals; Beagle; bioavailability; Biological Availability; blood; Cross-Over Studies; Dogs; experimental design; Female; females; Gels; Half-Life; high performance liquid chromatography; Hypnotics and Sedatives - administration & dosage; Hypnotics and Sedatives - pharmacokinetics; intranasal administration; Male; males; methylcellulose; Midazolam - administration & dosage; Midazolam - blood; Midazolam - pharmacokinetics; pharmacokinetics; Solutions
• ISSN: 0002-9645; 1943-5681
• DOI: 10.2460/ajvr.73.4.539

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. Animals: 10 (5 males and 5 females) healthy adult Beagles. Procedures: 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 and Clinical Relevance: IN administration of midazolam gel was superior to both IN and rectal administration of midazolam solution with respect to peak plasma concentration and bioavailability.