Pharmacokinetic study of oral amitriptyline in horses.
Abstract: The purpose of this study was to evaluate the pharmacokinetics of oral amitriptyline in horses. Oral amitriptyline (1 mg/kg) was administered to six horses. Blood samples were collected from jugular and lateral thoracic vein at predetermined times from 0 to 24 hr after administration. Plasma concentrations were determined by high-performance liquid chromatography and analyzed using noncompartmental methods. Pharmacodynamic parameters including heart rate, respiration rate, and intestinal motility were evaluated, and electrocardiographic examinations were performed in all subjects. The mean maximum plasma concentration (C ) of amitriptyline was 30.7 ng/ml, time to maximum plasma concentration (T ) 1-2 hr, elimination half-life (t ) 17.2 hr, area under plasma concentration-time curve (AUC) 487.4 ng ml hr , apparent clearance (Cl/F) 2.6 L hr kg , and apparent volume of distribution (Vd/F) 60.1 L/kg. Jugular vein sampling overestimated the amount of amitriptyline absorbed and should not be used to study uptake following oral administration. Heart rate and intestinal motility showed significant variation (p < .05). Electrocardiography did not provide conclusive results. Further studies are required to discern if multiple dose treatment would take the drug to steady state as expected, consequently increasing plasma concentrations.
© 2020 John Wiley & Sons Ltd.
Publication Date: 2020-04-27 PubMed ID: 32339314DOI: 10.1111/jvp.12870Google Scholar: Lookup
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Summary
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This study investigates the pharmacokinetics, or how the body processes a drug, specifically focusing on the drug amitriptyline when administered orally to horses. It also looks at how the drug affects certain physiological parameters, like heart rate and intestinal movement, in horses.
Methodology
A group of six horses were administered an oral dose of amitriptyline, a commonly used antidepressant in humans, of 1 mg per kg of body weight. After administration:
- Blood samples were collected at strategic time intervals between 0 to 24 hours. These were taken from two veins – the jugular and the lateral thoracic.
- Concentrations of amitriptyline in the plasma portions of the blood were measured using high-performance liquid chromatography, a technique used to separate and identify substances in a mixture.
- The data was then analysed via non-compartmental methods, a statistical procedure designed to gain insights from pharmacokinetic data sets.
- Pharmacodynamic parameters, which are indicators of how the drug may be affecting the body, including heart rate, respiration rate, and intestinal motility (movement), were measured.
- Electrocardiograms, or EKGs, were done to monitor heart activity.
Results
The results obtained from these tests and examinations provided insights into the absorption, distribution, metabolism, and elimination of amitriptyline in horses. Among the recorded data:
- The mean maximum plasma concentration of the drug (Cmax) was found to be 30.7 ng/mL,
- The average time it took to reach this maximum concentration (Tmax) was 1-2 hours,
- The half-life of the drug, or the time it takes for the concentration to decrease by half (t1/2), was around 17.2 hours.
- The area under the plasma concentration-time curve (AUC), a representation of the drug’s exposure over time, was 487.4 ng ml hr,
- The apparent clearance rate (Cl/F), signifying how quickly the drug is removed from the body, was 2.6 L hr kg,
- The apparent volume of distribution (Vd/F), inferring how the drug spread throughout the body, was 60.1 L/kg.
Samples taken from the jugular vein were found to overestimate the absorption of amitriptyline. Therefore, this method was deemed inappropriate for assessing uptake post-oral administration.
Analysis of the pharmacodynamic parameters showed significant variation in both heart rate and intestinal motility during the study period. However, the EKGs provided no conclusive results.
Conclusions and Further Research
While this study provides starting points for understanding how horses process amitriptyline, it concludes with the suggestion for further research. Specifically, the researchers highlight the need to determine if multiple doses of the drug would lead to a steady state, a point where the amount entering the body equals the amount being removed, thus increasing the overall plasma concentrations of the drug.
Cite This Article
APA
Recchi L, Alvariza S, Benech A, Ruiz N, José Estradé M, Suarez G, Crosignani N.
(2020).
Pharmacokinetic study of oral amitriptyline in horses.
J Vet Pharmacol Ther, 43(4), 381-384.
https://doi.org/10.1111/jvp.12870 Publication
Researcher Affiliations
- Department of Veterinary Pharmacology, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay.
- Department of Veterinary Pharmacology, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay.
- Department of Small Animal Medicine, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay.
- Department of Small Animal Medicine, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay.
- Department of Animal Reproduction, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay.
- Department of Veterinary Pharmacology, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay.
- Department of Veterinary Pharmacology, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay.
MeSH Terms
- Administration, Oral
- Amitriptyline / administration & dosage
- Amitriptyline / blood
- Amitriptyline / pharmacokinetics
- Animals
- Antidepressive Agents, Tricyclic / administration & dosage
- Antidepressive Agents, Tricyclic / blood
- Antidepressive Agents, Tricyclic / pharmacokinetics
- Area Under Curve
- Female
- Half-Life
- Horses / blood
- Horses / metabolism
- Male
Grant Funding
- Comisiu00f3n Sectorial de Investigaciu00f3n Cientu00edfica
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