FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Journal of veterinary pharmacology and therapeutics2020; 43(4); 381-384; doi: 10.1111/jvp.12870

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.
Get Full Text
Publication Date: 2020-04-27 PubMed ID: 32339314DOI: 10.1111/jvp.12870Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

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

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 43
Issue: 4
Pages: 381-384

Researcher Affiliations

Recchi, Lucciana
  • Department of Veterinary Pharmacology, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay.
Alvariza, Silvana
  • Department of Veterinary Pharmacology, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay.
Benech, Alejandro
  • Department of Small Animal Medicine, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay.
Ruiz, Natalie
  • Department of Small Animal Medicine, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay.
José Estradé, María
  • Department of Animal Reproduction, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay.
Suarez, Gonzalo
  • Department of Veterinary Pharmacology, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay.
Crosignani, Nadia
  • 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

References

This article includes 15 references
  1. Benbouzid M, Gavériaux-Ruff C, Yalcin I, Waltisperger E, Tessier LH, Muller A, Barrot M. Delta-opioid receptors are critical for tricyclic antidepressant treatment of neuropathic allodynia. Biological Psychiatry 63(6), 633-636.
    doi: 10.1016/j.biopsych.2007.06.016google scholar: lookup
  2. Dharmshaktu P, Tayal V, Kalra BS. Efficacy of antidepressants as analgesics: A review. The Journal of Clinical Pharmacology 52(1), 6-17.
    doi: 10.1177/0091270010394852google scholar: lookup
  3. Gozalo-Marcilla M, Luna SP, Crosignani N, Puoli Filho JN, Possebon FS, Pelligand L, Taylor PM. Sedative and antinociceptive effects of different combinations of detomidine and methadone in standing horses. Veterinary Anaesthesia and Analgesia 44(5), 1116-1127.
    doi: 10.1016/j.vaa.2017.03.009google scholar: lookup
  4. Khawam EA, Laurencic G, Malone DA. Side effects of antidepressants: An overview. Cleveland Clinic Journal of Medicine 73, 351-361.
    doi: 10.3949/ccjm.73.4.351google scholar: lookup
  5. Krystal JH, Sanacora G, Blumberg H, Anand A, Charney DS, Marek G, Mason GF. Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Molecular Psychiatry 7(S1), S71.
    doi: 10.1038/sj.mp.4001021google scholar: lookup
  6. Linden R, Antunes MV, Ziulkoski AL, Wingert M, Tonello P, Tzvetkov M, Souto AA. Determination of amitriptyline and its main metabolites in human plasma samples using HPLC-DAD: Application to the determination of metabolic ratios after single oral dose of amitriptyline. Journal of the Brazilian Chemical Society 19(1), 35-41.
    doi: 10.1590/s0103-50532008000100007google scholar: lookup
  7. Menzies-Gow N. ECG interpretation in the horse. Practice 23(8), 454-459.
    doi: 10.1136/inpract.23.8.454google scholar: lookup
  8. Messenger KM, Davis JL, LaFevers DH, Barlow BM, Posner LP. Intravenous and sublingual buprenorphine in horses: Pharmacokinetics and influence of sampling site. Veterinary Anaesthesia and Analgesia 38(4), 374-384.
    doi: 10.1111/j.1467-2995.2011.00613.xgoogle scholar: lookup
  9. Pedersen PJ, Kanters JK, Buhl R, Klaerke DA. Normal electrocardiographic QT interval in race-fit Standardbred horses at rest and its rate dependence during exercise. Journal of Veterinary Cardiology 15(1), 23-31.
    doi: 10.1016/j.jvc.2012.08.002google scholar: lookup
  10. Shen Y, Zhu R-H, Li H-D, Liu Y-W, Xu P. Validated LC-MS (ESI) assay for the simultaneous determination of amitriptyline and its metabolite nortriptyline in rat plasma: Application to a pharmacokinetic comparison. Journal of Pharmaceutical and Biomedical Analysis 53(3), 735-739.
    doi: 10.1016/j.jpba.2010.04.031google scholar: lookup
  11. Verdu B, Decosterd I, Buclin T, Stiefel F, Berney A. Antidepressants for the treatment of chronic pain. Drugs 68(18), 2611-2632.
    doi: 10.2165/0003495-200868180-00007google scholar: lookup
  12. Verheyen T, Decloedt A, De Clercq D, Deprez P, Sys S, van Loon G. Electrocardiography in horses, part 1: How to make a good recording. Vlaams Diergeneeskundig Tijdschrift 79(5), 331-336.
  13. Wang GK, Russell C, Wang SY. State-dependent block of voltage-gated Na+ channels by amitriptyline via the local anesthetic receptor and its implication for neuropathic pain. Pain 110(1-2), 166-174.
    doi: 10.1016/j.pain.2004.03.018google scholar: lookup
  14. Witchel HJ, Hancox JC, Nutt DJ. Psychotropic drugs, cardiac arrhythmia, and sudden death. Journal of Clinical Psychopharmacology 23(1), 58-77.
    doi: 10.1097/00004714-200302000-00010google scholar: lookup
  15. Yáñez JA, Remsberg CM, Sayre CL, Forrest ML, Davies NM. Flip-flop pharmacokinetics-delivering a reversal of disposition: Challenges and opportunities during drug development. Therapeutic Delivery 2(5), 643-672.
    doi: 10.4155/tde.11.19google scholar: lookup

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 100,151 horse owners like you who receive our email updates on horse health and nutrition.