Pharmacokinetics of midazolam after intravenous administration to horses.
Abstract: Midazolam is used to control seizures in horses and to enhance muscle relaxation, but its pharmacokinetics are unknown. Objective: To determine the pharmacokinetics and sedative effects of midazolam in horses. Methods: Blinded, randomised, crossover design. Methods: Midazolam was administered i.v. at either 0.05 or 0.1 mg/kg bwt to 6 horses on 2 occasions at least 7 days apart using a crossover design. Blood samples were collected before and at predetermined times through 24 h after administration. Serum midazolam concentrations were determined by a liquid chromatography tandem-mass spectrometry method. Heart and respiratory rates and indices of sedation, ataxia, and sensitivity to stimuli were recorded before and at predetermined times after midazolam administration. Results: Pharmacokinetic analysis was performed on samples from 5 horses in each group. Median total clearance was 10.6 ml/min/kg (range 6.1-15.2 ml/min/kg) and 10.4 ml/min/kg (range 8.4-17.6 ml/min/kg), and median volume of distribution at steady state was 2094 ml/kg (range 2076-2413 ml/kg) and 2822 ml/kg (range 2270-7064 ml/kg) after the 0.05 mg/kg and 0.1 mg/kg bwt doses, respectively. Median distribution half-life was 24 min (range 6-42 min) and 39 min (range 33.6-72 min) and median terminal half-life was 216 min (range 120-248 min) and 408 min (range 192-924 min) after the 0.05 mg/kg and 0.1 mg/kg bwt doses, respectively. Cardiorespiratory parameters and sedation scores did not change. Midazolam caused agitation, postural sway, weakness, and one horse became recumbent after the 0.1 mg/kg bwt dose. Conclusions: Midazolam produces ataxia and postural sway of short duration after i.v. administration to horses. Sedation was not evident after midazolam administration. Drug redistribution is likely the primary mechanism for the termination of effect. Conclusions: Midazolam produces muscle relaxation but not sedation in adult horses.
© 2013 EVJ Ltd.
Publication Date: 2013-03-12 PubMed ID: 23489241DOI: 10.1111/evj.12049Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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The study investigates the way in which the drug midazolam, used for treating seizures and enhancing muscle relaxation in horses, moves within the body and its effects on the animals. The conducted pharmacokinetic analysis and observed effects reveal that the drug can cause agitation, sway and weakness but it does not produce sedation in horses.
Methodology
The researchers used:
- A sample of 6 horses in a randomized, blinded, and crossover design.
- Two doses of midazolam were administered intravenously, one a 0.05 mg/kg body weight, the other 0.1 mg/kg body weight. The dosing was repeated on two occasions spaced at least a week apart.
- Blood samples were collected prior to and after drug administration at certain intervals over a 24 hour period.
- The concentration of midazolam in the serum was determined using liquid chromatography tandem-mass spectrometry.
- The heart and respiratory rates along with the horses reactions in terms of sedation, coordination impairment, and sensitivity to stimuli were recorded before and after the administration of midazolam.
Results
Findings of the pharmacokinetic analysis:
- Findings show that the clearance and volume of distribution fluctuated depending on the dosage of midazolam.
- Both the distribution half-life and terminal half-life of midazolam were longer when the administered dose was higher.
- There were no changes in cardiorespiratory parameters and sedation scores.
- However, high dose administration did result in symptoms such as agitation, postural sway, weakness, and one horse even became recumbent.
Conclusion
- Midazolam does not induce sedation in horses, despite it being noted for such effects in other creatures.
- It instead causes temporary ataxia (loss of full control of body movements), and postural sway in horses.
- The drug redistribution in the body is anticipated to be the prime mechanism for ending the effects of the drug.
- The drug is effective for muscle relaxation in adult horses.
Cite This Article
APA
Hubbell JA, Kelly EM, Aarnes TK, Bednarski RM, Lerche P, Liu Z, Lakritz J.
(2013).
Pharmacokinetics of midazolam after intravenous administration to horses.
Equine Vet J, 45(6), 721-725.
https://doi.org/10.1111/evj.12049 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine and The College of Pharmacy, The Ohio State University, USA.
MeSH Terms
- Anesthetics, Intravenous / administration & dosage
- Anesthetics, Intravenous / blood
- Anesthetics, Intravenous / pharmacokinetics
- Animals
- Area Under Curve
- Cross-Over Studies
- Female
- Half-Life
- Horses / blood
- Horses / metabolism
- Male
- Midazolam / administration & dosage
- Midazolam / blood
- Midazolam / pharmacokinetics
- Nevirapine / administration & dosage
- Nevirapine / blood
- Nevirapine / pharmacokinetics
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