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

Abstract

BACKGROUND:

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.

CONCLUSION:

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.

• Authors: Wolfgang Bäumer, Gudrun M Herrling, Karsten Feige
• Journal: BMC veterinary research (BMC Vet Res) Vol. 9 Pg. 158 (Aug 09 2013) ISSN: 1746-6148 [Electronic] England
• PMID: 23938183 (Publication Type: Journal Article)

Chemical References

• Fibrinolytic Agents
• Fibrinogen
• Tissue Plasminogen Activator

Topics

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