Eagleson Joseph S, Platt Simon R, Strong Deborah L Elder, Kent Marc, Freeman Anne C, Nghiem Peter P, Zheng Bo, White Catherine A
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Am J Vet Res. 2012 Apr;73(4):539-45. doi: 10.2460/ajvr.73.4.539.
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.
10 (5 males and 5 females) healthy adult Beagles.
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.
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.
IN administration of midazolam gel was superior to both IN and rectal administration of midazolam solution with respect to peak plasma concentration and bioavailability.
比较咪达唑仑新型生物黏附凝胶制剂经鼻内（IN）给药后的药代动力学与咪达唑仑溶液经鼻内、静脉内（IV）和直肠给药后在犬体内的药代动力学。
10只（5只雄性和5只雌性）健康成年比格犬。
将犬分配到4个治疗组进行交叉研究设计。最初，给第1组静脉注射咪达唑仑溶液（5mg/mL）（0.2mg/kg），给第2组直肠给药，给第3组经鼻内给药；给第4组经鼻内给药0.4%羟丙基甲基纤维素咪达唑仑凝胶制剂（50mg/mL）（0.2mg/kg）。每只犬接受所有4种治疗；后续治疗之间有7天的洗脱期。在咪达唑仑给药前后采集血样。使用高效液相色谱法测定血浆中咪达唑仑的浓度。
凝胶制剂经鼻内给药后的血浆峰浓度显著高于溶液经鼻内和直肠给药后的血浆峰浓度。达到峰浓度的平均±标准差时间分别为11.70±2.63分钟（凝胶经鼻内给药）、17.50±2.64分钟（溶液经鼻内给药）和39±14.49分钟（溶液直肠给药）。咪达唑仑的平均生物利用度分别为70.4%（凝胶经鼻内给药）、52.0%（溶液经鼻内给药）和49.0%（溶液直肠给药）。凝胶制剂经鼻内给药后的生物利用度显著高于溶液经鼻内和直肠给药后的生物利用度。
在血浆峰浓度和生物利用度方面，咪达唑仑凝胶经鼻内给药优于咪达唑仑溶液经鼻内和直肠给药。
