Pharmacokinetics of Remimazolam Versus Midazolam After Intravenous Administration to Horses

Remimazolam (RMZ) is a new short-half-life benzodiazepine used in humans. We compared the pharmacokinetics and sedative effects of RMZ with those of midazolam (MDZ) in Thoroughbred horses. Six Thoroughbreds received a single IV dose of RMZ 0.05 mg/kg or MDZ 0.05 mg/kg in a randomized crossover design. Blood samples were collected, and plasma RMZ and MDZ concentrations were measured by LC-MS/MS. Plasma concentrations were analyzed by using non-compartmental analysis and a nonlinear mixed effect model. The half-life of RMZ (0.77 ± 0.15 h) was significantly shorter than that of MDZ (3.7 ± 0.3 h). The bootstrap estimates of the parameters (mean ± SD) for RMZ and MDZ were 14.0 ± 1.1 L/kg/h and 0.45 ± 0.02 L/kg/h for clearance; 2.01 ± 0.26 L/kg and 1.31 ± 0.10 L/kg for the distribution volume of steady state. RMZ clearance was significantly higher than MDZ clearance in a comparison of post hoc values for the six horses. Wobble, observed as muscle relaxation/ataxia and a diminished stimulus response to RMZ, was observed from immediately after administration until 5 min later; the response generally disappeared after 10 min. Clinical trials will determine the place of RMZ in total intravenous anesthesia for rapid and smooth recovery in horses.