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BMC veterinary research2013; 9; 158; doi: 10.1186/1746-6148-9-158

Pharmacokinetics and thrombolytic effects of the recombinant tissue-type plasminogen activator in horses.

Abstract: To test the efficacy of the recombinant tissue-type plasminogen activator (rt-PA) alteplase in horses, the thrombolytic effect was tested in in vitro generated equine thrombi. The extent of lysis was determined by measuring the decrease in thrombi weight over a period of 4 hours. In vivo pharmacokinetics of alteplase were determined in 6 healthy horses. A single dose (1 mg/kg) was applied via intravenous infusion over a period of 30 minutes Coagulation-related variables, blood count and clinical parameters were taken before the treatment and until 48 h after treatment. In addition, plasma rt-PA concentration was measured until 300 min after commencing the infusion. Results: In vitro, a dose dependent decrease of thrombus weight ranging from a 56 (± 6.5) % decrease for 0.5 μg/ml to 92 (± 2.1) % decrease for 5 μg/ml rt-PA was noted. The D-dimer concentration in the lysis medium correspondingly increased from 0.10 up to 10.8 mg/l. In vivo, none of the horses showed an adverse reaction to the alteplase infusion. In some horses blood parameters were slightly altered. The 1 mg/kg dose yielded the following pharmacokinetic parameters: Cmax = 1.25 ± 0.27 μg/ml; CL = 21.46 ± 5.67 ml/min/kg; dominant half life (t1/2α) = 6.81 ± 1.48 minutes; median elimination half life (t1/2β) = 171 min (range: 85–1061); AUC = 50.33 ± 17.62 μg · min /ml. Conclusions: These findings indicate that a single dose of 1 mg/kg alteplase results in rt-PA plasma concentrations comparable to those in humans and might be sufficient for a thrombolytic therapy in horses. Further studies must be performed to determine the alteplase effectiveness in horses with jugular vein thrombosis.
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Publication Date: 2013-08-09 PubMed ID: 23938183PubMed Central: PMC3750949DOI: 10.1186/1746-6148-9-158Google Scholar: Lookup
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  • 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 research investigates the effectiveness of a drug known as recombinant tissue-type plasminogen activator (rt-PA) alteplase for dissolving blood clots in horses. Both laboratory tests and tests on living animals were conducted, showing promising results, although further research is necessary, particularly in horses with jugular vein thrombosis.

Methodology

  • The researchers examined the clot-destroying effect of rt-PA in a controlled laboratory setting, testing on clots formed using horse blood.
  • They introduced varying doses of rt-PA to these clots and documented the reduction in clot size over a 4-hour period.
  • The effectiveness of the drug was also determined by measuring an element called D-dimer present after clot breakdown.

In Vivo Testing

  • Six healthy horses were given an intravenous infusion of rt-PA and observed for any adverse reaction.
  • Different blood parameters were monitored before and up to 48 hours after administering the drug.
  • The rt-PA concentrations in plasma were measured up to 300 minutes after starting the infusion.
  • The goal was to calculate pharmacokinetic parameters including maximum concentration of the drug (Cmax), its clearance rate (CL), the half-time it takes for its concentration to decrease by half (t1/2α) and median elimination half life (t1/2β), and the area under the plasma concentration-time curve (AUC).

Findings

  • In the laboratory-based portion of the study, researchers noticed a significant reduction in clot size depending upon the dose of rt-PA provided, with a maximum reduction of 92%.
  • D-dimer concentration in the medium increased with the dosage, indicating successful clot breakdown.
  • In living horses, no adverse reaction was observed following the administration of rt-PA. Some minor changes were seen in blood parameters, likely due to the drug’s effects.
  • A single dose of the drug resulted in plasma concentrations similar to those seen in human applications of the medication, suggesting it may be beneficial for clot treatment in horses.

Conclusions

  • The findings of this study suggest that rt-PA could be a viable treatment for blood clots in horses, but further study is required. Promising results emerged, particularly with a single dose of 1 mg/kg, but the research team recommends additional testing, specifically on horses suffering from jugular vein thrombosis.

Cite This Article

APA
Bäumer W, Herrling GM, Feige K. (2013). Pharmacokinetics and thrombolytic effects of the recombinant tissue-type plasminogen activator in horses. BMC Vet Res, 9, 158. https://doi.org/10.1186/1746-6148-9-158

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 9
Pages: 158

Researcher Affiliations

Bäumer, Wolfgang
    Herrling, Gudrun M
      Feige, Karsten

        MeSH Terms

        • Animals
        • Area Under Curve
        • Female
        • Fibrinogen / analysis
        • Fibrinolytic Agents / administration & dosage
        • Fibrinolytic Agents / pharmacokinetics
        • Fibrinolytic Agents / therapeutic use
        • Half-Life
        • Horses / metabolism
        • Infusions, Intravenous / veterinary
        • Male
        • Partial Thromboplastin Time / veterinary
        • Prothrombin Time / veterinary
        • Thrombin Time / veterinary
        • Thrombosis / drug therapy
        • Thrombosis / veterinary
        • Tissue Plasminogen Activator / administration & dosage
        • Tissue Plasminogen Activator / pharmacokinetics
        • Tissue Plasminogen Activator / therapeutic use

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        Citations

        This article has been cited 5 times.
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