Oral reserpine administration in horses results in low plasma concentrations that alter platelet biology.
Abstract: Reserpine is a popular drug in the equine industry for long-term tranquilisation. Clinical observations revealed that blood from horses receiving oral reserpine was hypercoagulable. No studies have documented the pharmacokinetics of orally administered reserpine nor the effects of reserpine on platelets in horses. Objective: To evaluate the pharmacokinetics of oral reserpine in horses and the effects of clinically relevant concentrations of reserpine on platelet functionality in vitro. Methods: Experimental controlled study. Methods: The pharmacokinetics of oral reserpine (2.5 mg/horse, once) were determined in six healthy adult horses. Plasma samples were collected and concentrations of reserpine were determined by UPLC-MS/MS. Using this data, the in vitro effects of reserpine on platelets were examined. Aggregation, adhesion and releasate assays for serotonin and thromboxane B were performed on platelets exposed to varying concentrations of reserpine (0.01-10 ng/mL), aspirin (negative control) and saline (unexposed control). Results: Oral reserpine administration demonstrated low plasma concentrations with a C of 0.2 ± 0.06 ng/mL and a prolonged half-life of 23.6 ± 6.24 h. Simulations over a dose range of 2-8 μg/kg predicted C at steady state between 0.06-0.9 ng/mL. Platelets exposed to these reserpine concentrations in vitro displayed increased aggregation and adhesion compared to unexposed or aspirin-exposed platelets as well as compared to higher concentrations of reserpine. These functional changes correlated with lower concentrations of serotonin and higher concentrations of thromboxane B in the platelet suspension supernatant. Conclusions: This study used a small number of horses and only in vitro platelet experiments. Conclusions: Oral reserpine demonstrates low plasma concentrations and a prolonged half-life in horses. At these concentrations, reserpine causes significant changes in platelet function, most likely due to serotonin release and re-uptake which primes platelets for activation and thromboxane B release. These findings suggest that clinicians should harvest blood for biological processing prior to the onset of reserpine administration.
© 2018 EVJ Ltd.
Publication Date: 2018-12-14 PubMed ID: 30465727DOI: 10.1111/evj.13048Google Scholar: Lookup
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- Clinical Trial
- Veterinary
- Journal Article
Summary
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This research investigates the effects of the drug reserpine on horses, specifically its impact on platelet function and blood coagulation. The findings indicate that reserpine, commonly used for long-term tranquilisation, leads to low plasma concentrations and extensive platelet activity in horses.
Methodology
- The research was carried out as an experimental controlled study.
- The researchers administered oral doses of reserpine (2.5 mg per horse, once only) to six healthy adult horses, then studied the pharmacokinetics – how the drug is absorbed, distributed, metabolized, and excreted by the body.
- Plasma samples were collected and the concentrations of reserpine were determined using precise analytical methods (UPLC-MS/MS).
- The researchers then analyzed the impact of various concentrations of reserpine on platelets – components of blood that aid coagulation – by conducting aggregation, adhesion, and releasate assays.
- These assays tested for serotonin and thromboxane B, substances that influence platelet function, in platelets exposed to reserpine. Aspirin was used as a negative control and saline for the unexposed control.
Results
- Administering oral reserpine led to low plasma concentrations and a prolonged half-life in horses. The half-life of a drug refers to how long it takes for the concentration of the drug in the body to reduce by half – in this case, it was 23.6 hours on average.
- Platelets exposed to reserpine showed increased adhesion and aggregation compared to control groups. They also exhibited different levels of serotonin and thromboxane B, compared to those not exposed to reserpine or exposed to higher reserpine concentrations.
Conclusions
- The study suggests that even with low plasma concentrations, reserpine can significantly alter platelets’ function in horses, likely due to the impact on serotonin release and reuptake.
- Such changes potentially prime platelets for activation and the release of thromboxane B, which leads to the evident hypercoagulability in the horses’ blood.
- The findings suggest that blood harvest for biological processing should occur before the administration of reserpine to prevent its effects on platelets.
- However, the small sample size and the exclusive use of in vitro platelet experiments restrict the generalizability of the results. Further studies will be needed to fully understand the effects of reserpine in a clinical setting.
Cite This Article
APA
Gilbertie JM, Davis JL, Davidson GS, McDonald AM, Schirmer JM, Schnabel LV.
(2018).
Oral reserpine administration in horses results in low plasma concentrations that alter platelet biology.
Equine Vet J, 51(4), 537-543.
https://doi.org/10.1111/evj.13048 Publication
Researcher Affiliations
- Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, USA.
- Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
- Clinical Pharmacy Services, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
- Clinical Pharmacy Services, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
- Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, USA.
- Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, USA.
MeSH Terms
- Administration, Oral
- Adrenergic Uptake Inhibitors / administration & dosage
- Adrenergic Uptake Inhibitors / blood
- Adrenergic Uptake Inhibitors / pharmacokinetics
- Adrenergic Uptake Inhibitors / pharmacology
- Animals
- Area Under Curve
- Blood Platelets / drug effects
- Female
- Half-Life
- Horses / blood
- Male
- Reserpine / administration & dosage
- Reserpine / blood
- Reserpine / pharmacokinetics
- Reserpine / pharmacology
Grant Funding
- Orthopedic Research in honour of Gus
- Equine athletes
Citations
This article has been cited 5 times.- Camargo Garbin L, Morris MJ. A Comparative Review of Autologous Conditioned Serum and Autologous Protein Solution for Treatment of Osteoarthritis in Horses. Front Vet Sci 2021;8:602978.
- Velloso Alvarez A, Boone LH, Braim AP, Taintor JS, Caldwell F, Wright JC, Wooldridge AA. A Survey of Clinical Usage of Non-steroidal Intra-Articular Therapeutics by Equine Practitioners. Front Vet Sci 2020;7:579967.
- Satué K, Gardon JC, Muñoz A. Clinical and laboratorial description of the differential diagnoses of hemostatic disorders in the horse. Iran J Vet Res 2020 Winter;21(1):1-8.
- Gilbertie JM, Schnabel LV, Hickok NJ, Jacob ME, Conlon BP, Shapiro IM, Parvizi J, Schaer TP. Equine or porcine synovial fluid as a novel ex vivo model for the study of bacterial free-floating biofilms that form in human joint infections. PLoS One 2019;14(8):e0221012.
- Page AE, Johnson M, Parker JL, Jacob O, Poston R, Adams AA, Adam EN. The Effects of Intra-Articular Triamcinolone and Autologous Protein Solution on Metabolic Parameters in Horses. Animals (Basel) 2024 Aug 2;14(15).
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