Pharmacokinetics and metabolism of amitraz in ponies and sheep.
Abstract: Amitraz and its active metabolite BTS27271 were given intravenously to ponies and sheep at equimolar doses of 1 mg/kg and 0.68 mg/kg, respectively, and the plasma concentrations of amitraz and BTS27271 estimated at various times thereafter. Amitraz was hydrolysed to BTS27271 in both species. Amitraz was undetectable in sheep plasma after approximately 5 min but persisted in the plasma of ponies for at least 90 min. The persistence of unmetabolized amitraz in ponies may have implications for the toxicity of amitraz in that species. The primary and secondary disposition half-lives of amitraz in ponies were 2 and 39 min, respectively. BTS27271 was distributed rapidly outside the plasma in both species with a primary disposition half-life of 4.4 min in sheep and 5.9 min in ponies. The secondary disposition half-lives were 51 and 55 min, respectively. The secondary phase of the disposition of BTS27271 was similar whether BTS27271 was given directly or derived by hydrolysis from amitraz. However, significant differences were evident in the primary phase of the disposition of BTS27271. Sheep demonstrated a larger apparent volume of distribution of BTS27271 than ponies and more rapid body clearance.
Publication Date: 1995-06-01 PubMed ID: 7674457DOI: 10.1111/j.1365-2885.1995.tb00580.xGoogle Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research studied the rate and manner in which the drug amitraz and its metabolite BTS27271 are processed and cleared from the body in ponies and sheep. Elevated levels of amitraz were observed in ponies, which could indicate possible toxicity risks.
Study Design and Procedure
- The researchers administered amitraz and BTS27271 intravenously to both ponies and sheep at doses of 1 mg/kg and 0.68 mg/kg, respectively.
- The concentration levels of both substances in the plasma of the subjects were then monitored and recorded at different intervals after the administration of the drugs.
Findings and Observations
- It was found that amitraz was metabolized into BTS27271 in both ponies and sheep.
- However, the processing of amitraz differed between the two species; it became undetectable in sheep plasma approximately five minutes after administration but remained detectable in the plasma of ponies for at least 90 minutes.
- The primary and secondary half-lives (the times required for the concentration of the drug to be reduced by half in the body) of amitraz were found to be 2 minutes and 39 minutes in ponies, respectively.
- BTS27271 was quickly distributed outside of the plasma in both species and demonstrated primary disposition half-lives of 4.4 minutes in sheep and 5.9 minutes in ponies.
- This study observed similar secondary phase of disposition for BTS27271 in both species, irrespective of whether it was directly injected into the body or derived by the hydrolysis of amitraz.
- Conversely, primary phase differences were observed; sheep showed a larger apparent volume of distribution of BTS27271 than ponies, and their body cleared the substance more rapidly.
Implications of the Findings
- The results suggest possible variance in the toxicity and side effects of amitraz in different species due to the observed differences in metabolism, distribution, and clearance mechanisms.
- Particularly, the sustained presence of amitraz in ponies’ plasma suggests potential risks of toxicity for this species, which requires further investigation.
Cite This Article
APA
Pass MA, Mogg TD.
(1995).
Pharmacokinetics and metabolism of amitraz in ponies and sheep.
J Vet Pharmacol Ther, 18(3), 210-215.
https://doi.org/10.1111/j.1365-2885.1995.tb00580.x Publication
Researcher Affiliations
- Department of Physiology and Pharmacology, University of Queensland, St. Lucia, Australia.
MeSH Terms
- Absorption
- Amidines / pharmacokinetics
- Animals
- Female
- Half-Life
- Horses / metabolism
- Hydrolysis
- Injections, Intravenous / veterinary
- Insecticides / pharmacokinetics
- Male
- Sheep / metabolism
- Toluidines / pharmacokinetics
Citations
This article has been cited 2 times.- Nanjundappa S, Nair SN, Udayan D, Kanapadinchareveetil S, Jacob M, Ravindran R, Juliet S. Disposition Kinetics of Amitraz in Lactating Does. Molecules 2021 Aug 6;26(16).
- Sparks DS, Saifzadeh S, Savi FM, Dlaska CE, Berner A, Henkel J, Reichert JC, Wullschleger M, Ren J, Cipitria A, McGovern JA, Steck R, Wagels M, Woodruff MA, Schuetz MA, Hutmacher DW. A preclinical large-animal model for the assessment of critical-size load-bearing bone defect reconstruction. Nat Protoc 2020 Mar;15(3):877-924.
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