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Updated: Aug 5, 2026

Ferric Chloride-induced Murine Thrombosis Models
10:37

Ferric Chloride-induced Murine Thrombosis Models

Published on: September 5, 2016

Dose-dependent thrombolysis, pharmacokinetics and hemostatic effects of recombinant human tissue-type plasminogen

H D Garabedian, H K Gold, R C Leinbach

    The American Journal of Cardiology
    |October 1, 1986
    PubMed

    The pharmacokinetics, thrombolytic profile and effects on hemostasis of graded intravenous doses of recombinant human tissue-type plasminogen activator (rt-PA) were studied in 45 patients with acute myocardial infarction. Infusion of rt-PA at a rate of 4 to 8.3 micrograms/kg/min resulted in plateau levels of the drug in plasma of 0.52 to 1.4 micrograms/ml. A linear relation between infusion rate and plasma rt-PA concentration was observed, although plasma drug levels varied substantially among subjects who received infusions at the same rate. The ratio between plateau levels of rt-PA in plasma and infusion rate was inversely related to initial distribution volume (7.3 +/- 2.9 liters, n = 21). The decline in plasma concentration of rt-PA, x(t), as a function of time after cessation of the infusion, was described adequately by the biexponential equation: x(t) = 0.71exp(-0.13t) + 0.29exp(-0.015t). The initial and terminal half-lives of rt-PA in the blood were 5.3 +/- 1.7 and 46.2 +/- 14 minutes, respectively. The efficacy of rt-PA for coronary thrombolysis was dose-dependent. With 4 micrograms/kg/min of rt-PA for 90 minutes, no reperfusion was achieved, whereas infusion rates of 5 micrograms/kg/min or more for 90 minutes accomplished reperfusion in more than 80% of the patients. However, the frequency of occurrence of residual intraluminal thrombus was significantly lower with an infusion rate of 7 micrograms/kg/min for 90 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

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