A pharmacokinetic study of midazolam in dogs: nasal drop vs. atomizer administration.

PURPOSE The purpose of this investigation was to compare the pharmacokinetics of midazolam following intravenous, intranasal drop, and nasal-atomizer administration in beagle dogs. METHODS Six animals weighing 9-13 kg were used in a repeated-measure design, group assignment based on route of drug administration. Midazolam (1.5 mg/kg) was administered with the delivery route based on group assignment. Blood samples were obtained at baseline and at 1, 3, 5, 7, 10, 15, 20, 30, and 45 min after administration. Cerebrospinal fluid samples (CSF) were obtained at 5 and 10 min after administration. Plasma and CSF concentrations of midazolam were determined by electron-capture gas-liquid chromatography. RESULTS Comparison between groups and over time demonstrated that both nasal routes resulted in significantly higher CSF concentrations relative to corresponding plasma levels, and that nasal-atomizer administration produced significantly higher CSF concentrations compared to the drop approach.