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

Abstract

BackgroundTo 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.ResultsIn 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.ConclusionThese 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.

Management of free flap salvage using thrombolytic drugs: A systematic review

“…Although the induction of antibodies to urokinase has not been reported, doses greater than 250,000 IU can induce tachycardia and shaking/chillness. 32 A recent in vitro thrombolysis study reported a dose-dependent decrease in thrombus weight induced by t-PA. 48 Addition of more than 3 μg/mL t-PA at the site of an in vitro generated thrombus did not result in a significant increase of thrombolytic activity and thus might be taken as a breakpoint and maximal plasma concentration to be achieved. Based on these findings, it is advocated to administer 1 mg/kg t-PA for optimal lysis of thrombi when infusing systemically.…”

Complications of intravenous catheterization in horses

“…Recombinant tissue plasminogen activator has recently been evaluated in vivo and in vitro for its thrombolytic effects in healthy horses. While initial results appear promising more studies are needed to evaluate the safety and effectiveness (Baumer et al, 2013).…”

Anterograde Injection of Alteplase Salvages Deep Inferior Epigastric Perforator Flap in Reconstructive Breast Surgery

“…Baumer et al reported in their in vitro thrombolysis study a dose dependent decrease in thrombus weight induced by rt-PA. Based on these findings, it is recommended to administer no more than 1 mg/kg rt-PA for optimal lysis of thrombi when infusing systemically. 15–17…”