Pharmacokinetics and fibrin specificity of alteplase during accelerated infusions in acute myocardial infarction
Autor: | Karl-Ludwig Neuhaus, Jarosław Wójcik, Liane Gläsle-Schwarz, P. Tanswell, Ulrich Tebbe, Erhard Seifried |
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Rok vydání: | 1992 |
Předmět: |
Male
Time Factors medicine.medical_treatment Myocardial Infarction Infarction Fibrin Substrate Specificity Pharmacokinetics Humans Medicine alpha-Macroglobulins Fibrinolysin Myocardial infarction Infusions Intravenous Aged Hemostasis alpha-2-Antiplasmin Chemotherapy biology business.industry Fibrinogen Plasminogen Middle Aged medicine.disease Regimen Anistreplase Tissue Plasminogen Activator Anesthesia biology.protein Female business Cardiology and Cardiovascular Medicine Plasminogen activator medicine.drug |
Zdroj: | Journal of the American College of Cardiology. 19(5):1071-1075 |
ISSN: | 0735-1097 |
DOI: | 10.1016/0735-1097(92)90297-z |
Popis: | Pharmacokinetics and fibrin specificity of alteplase (recombinant tissue-type plasminogen activator) were determined in 10 patients with acute myocardial infarction undergoing an accelerated infusion regimen during the alteplase/anistreplase patency study (TAPS). Fifteen milligrams of alteplase was administered as an intravenous bolus injection, followed by infusions of 50 mg over 30 min and 35 mg over a further 60 min. Mean steady state plasma concentrations of alteplase during the initial 30 min were 3.2 +/- 0.84 micrograms/ml, measured immunochemically, and 2.1 +/- 0.23 micrograms/ml, measured using a functional activity assay. These values were 45% and 51% higher, respectively, than those during the standard infusion schedule (p less than 0.01). However, the predominant plasma half-life determined by model fitting based on either assay (3.3 to 3.5 min) was unaltered compared with the standard regimen. Maximal concentrations of fibrin and fibrinogen degradation products were 5.1 +/- 2.2 and 1.9 +/- 1.1 micrograms/ml, respectively. Plasminogen decreased to 70% and alpha 2-antiplasmin to 35% of values before infusion. The results indicate that 1) improved coronary patency rates during "front-loaded" infusions can be rationalized in terms of higher plasma concentrations of both free and immunoreactive alteplase, 2) kinetic variables are comparable with those of other dosing strategies, and 3) fibrin specificity is not diminished relative to that of the standard infusion regimen. |
Databáze: | OpenAIRE |
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