Lacoste L, Bouquet S, Ingrand P, Caritez J C, Carretier M, Debaene B
Department of Genetics, INRA le Magneraud, University of Poitiers School of Medicine, France.
Lab Anim. 2000 Jan;34(1):29-35. doi: 10.1258/002367700780578073.
Intranasal midazolam was studied in two series of piglets: series 1, n = 20 (18 +/- 3 kg), a randomized double blind pharmacodynamic study to compare doses of 0.2 mg/kg and 0.4 mg/kg; series 2, n = 9 (42 +/- 8 kg), a pharmacokinetic study with a 0.4 mg/kg dose administered either intravenously (i.v.) or intranasally (i.n.) in a cross-over protocol with a one-week wash-out period between each. In series 1, midazolam caused significant anxiolysis and sedation within 3 to 4 min, without a significant difference between 0.2 and 0.4 mg/kg doses for any of the studied parameters. In series 2, after intranasal midazolam administration of 0.4 mg/kg, plasma concentrations attained a maximum (Cmax) of 0.13 +/- 0.04 mg/l at 5 min (median Tmax) and remained higher than 0.04 mg/l until 60 min. The bioavailability factor (F) in this study was F = 0.64 +/- 0.17 by the intranasal route. The terminal half-life (T1/2 lambda z) = 145 +/- 138 min was comparable with the i.v. administration half-life (158 +/- 127 min). In conclusion, optimal intranasal midazolam dose in piglets was 0.2 mg/kg, which procures rapid and reliable sedation, adapted to laboratory piglets.
第1组，n = 20（体重18±3千克），一项随机双盲药效学研究，比较0.2毫克/千克和0.4毫克/千克的剂量；第2组，n = 9（体重42±8千克），一项药代动力学研究，采用交叉方案，以0.4毫克/千克的剂量静脉注射（i.v.）或鼻内给药（i.n.），每次给药之间有一周的洗脱期。在第1组中，咪达唑仑在3至4分钟内引起显著的抗焦虑和镇静作用，在所研究的任何参数方面，0.2毫克/千克和0.4毫克/千克剂量之间均无显著差异。在第2组中，鼻内给予0.4毫克/千克咪达唑仑后，血浆浓度在5分钟（中位数Tmax）时达到最大值（Cmax）为0.13±0.04毫克/升，并在60分钟内一直高于0.04毫克/升。本研究中鼻内给药途径的生物利用度因子（F）为F = 0.64±0.17。终末半衰期（T1/2λz）= 145±138分钟，与静脉注射给药的半衰期（158±127分钟）相当。总之，仔猪鼻内给予咪达唑仑的最佳剂量为0.2毫克/千克，可产生快速且可靠的镇静作用，适用于实验用仔猪。
