Pharmacokinetics and fibrin specificity of alteplase during accelerated infusions in acute myocardial infarction

• Published in: Journal of the American College of Cardiology Vol. 19; no. 5; pp. 1071 - 1075
• Main Authors: Tanswell, Paul, Tebbe, Ulrich, Neuhaus, Karl-Ludwig, Gläsle-Schwarz, Liane, Wojcik, Jaroslaw, Seifried, Erhard
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-04-1992; Elsevier Science
• Subjects: Aged; alpha-2-Antiplasmin - analysis; alpha-Macroglobulins - analysis; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Female; Fibrin - analysis; Fibrin - metabolism; Fibrinogen - analysis; Fibrinolysin - analysis; Hemostasis - drug effects; Humans; Infusions, Intravenous - methods; Male; Medical sciences; Middle Aged; Myocardial Infarction - blood; Myocardial Infarction - drug therapy; Pharmacology. Drug treatments; Plasminogen - analysis; Substrate Specificity; Time Factors; Tissue Plasminogen Activator - administration & dosage; Tissue Plasminogen Activator - blood; Tissue Plasminogen Activator - metabolism; Tissue Plasminogen Activator - pharmacokinetics; Tissue Plasminogen Activator - pharmacology; Human; Chemotherapy; Rapid technique; Treatment; Intravenous administration; Infarct; Myocardium; Cardiovascular disease; Pharmacokinetics; Coronary heart disease; Fibrinolytic
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/0735-1097(92)90297-Z

Pharmacokinetics and fibrin specificity of alteplase (recombinant tissue-type plasminogen activator) were determined in 10 patients with acute myocardiol 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 μg/ml, measured immunochemically, and 2.1 ± 0.23 μg/ml, measured using a functional activity assay. These values were 45% and 51% higher, respectively, than those during the standard infusion schedule (p < 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 μg/ml, respectively. Plasminogen decreased to 70% and alpha2-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.