Pharmacokinetics of Remimazolam Versus Midazolam After Intravenous Administration to Horses.
Abstract: 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.
© 2025 John Wiley & Sons Ltd.
Publication Date: 2025-10-07 PubMed ID: 41055126DOI: 10.1111/jvp.70030Google Scholar: Lookup
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- Journal Article
Summary
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Overview
- This study compares the pharmacokinetics and sedative effects of two benzodiazepine drugs, Remimazolam (RMZ) and Midazolam (MDZ), after intravenous administration in horses.
- The goal was to understand how RMZ, a newer short-acting drug, behaves in horses compared to the commonly used MDZ, and to evaluate its potential for use in veterinary anesthesia.
Study Design and Methods
- Subject Animals: Six Thoroughbred horses were selected for the study.
- Drug Administration: Each horse received a single intravenous dose of either RMZ (0.05 mg/kg) or MDZ (0.05 mg/kg) following a randomized crossover design, meaning each horse received both drugs at different times.
- Sampling: Blood samples were collected from the horses after drug administration to measure the plasma concentrations of RMZ and MDZ.
- Analysis Techniques:
- Plasma concentrations of both drugs were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a precise analytical method.
- Pharmacokinetic analysis was performed using both non-compartmental methods and a nonlinear mixed-effect model to estimate parameters such as half-life, clearance, and volume of distribution.
Pharmacokinetic Findings
- Half-Life:
- Remimazolam had a significantly shorter half-life (0.77 ± 0.15 hours) compared to Midazolam (3.7 ± 0.3 hours), indicating faster elimination from the body.
- Clearance:
- Remimazolam showed a much higher clearance rate (14.0 ± 1.1 L/kg/h) relative to Midazolam (0.45 ± 0.02 L/kg/h), meaning the drug was removed from the plasma more rapidly.
- Volume of Distribution at Steady State (Vdss):
- RMZ had a larger volume of distribution (2.01 ± 0.26 L/kg) versus MDZ (1.31 ± 0.10 L/kg), suggesting greater distribution in body tissues.
Pharmacodynamic Observations
- The sedative effects were noted primarily by observing “wobble,” which includes muscle relaxation and ataxia along with a diminished response to stimuli immediately after drug administration.
- This wobble effect was noticeable right after RMZ injection but generally resolved within 10 minutes.
Implications and Future Directions
- The rapid clearance and short half-life of RMZ suggest advantages for using it in total intravenous anesthesia protocols in horses, especially where quick and smooth recovery is important.
- The study highlights the potential role of RMZ as a sedative with better controllability and less prolonged sedation compared to MDZ.
- Future clinical trials are necessary to firmly establish the safety, efficacy, and optimal dosing strategies of RMZ in equine anesthesia.
Cite This Article
APA
Kawashima M, Kuroda T, Minamijima Y, Yamazaki Y, Mita H, Nomura M, Ohta M.
(2025).
Pharmacokinetics of Remimazolam Versus Midazolam After Intravenous Administration to Horses.
J Vet Pharmacol Ther, 49(1), 94-98.
https://doi.org/10.1111/jvp.70030 Publication
Researcher Affiliations
- Miho Training Center Racehorse Clinic, Japan Racing Association, Ibaraki, Japan.
- Equine Research Institute, Japan Racing Association, Tochigi, Japan.
- Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Japan.
- Drug Analysis Department, Laboratory of Racing Chemistry, Utsunomiya, Japan.
- Equine Research Institute, Japan Racing Association, Tochigi, Japan.
- Equine Research Institute, Japan Racing Association, Tochigi, Japan.
- Equine Research Institute, Japan Racing Association, Tochigi, Japan.
- Equine Research Institute, Japan Racing Association, Tochigi, Japan.
MeSH Terms
- Animals
- Horses / blood
- Horses / metabolism
- Midazolam / pharmacokinetics
- Midazolam / blood
- Midazolam / administration & dosage
- Hypnotics and Sedatives / pharmacokinetics
- Hypnotics and Sedatives / blood
- Hypnotics and Sedatives / administration & dosage
- Cross-Over Studies
- Half-Life
- Male
- Benzodiazepines / pharmacokinetics
- Benzodiazepines / blood
- Benzodiazepines / administration & dosage
- Female
- Injections, Intravenous / veterinary
- Administration, Intravenous / veterinary
- Area Under Curve
Grant Funding
- Japan Racing Association
References
This article includes 21 references
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