Clinical pharmacology in patients with evolving myocardial infarction of tissue-type plasminogen activator produced by recombinant DNA technology

This study was performed to characterize selected pharmacologic properties and effects on the fibrinolytic system of tissue-type plasminogen activator synthesized by recombinant DNA technology (rt-PA) in 12 patients treated for coronary thrombosis. rt-PA was infused parenterally (by the intracoronar...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 1985, Vol.71 (1), p.110-116
Main Authors: TIEFENBRUNN, A. J, ROBISON, A. K, KURNIK, P. B, LUDBROOK, P. A, SOBEL, B. E
Format: Article
Language:English
Subjects:
Adult
Aged
alpha-2-Antiplasmin - metabolism
Biological and medical sciences
Blood Coagulation
Blood. Blood coagulation. Reticuloendothelial system
DNA, Recombinant
Female
Fibrinogen - metabolism
Fibrinolysis
Half-Life
Humans
Kinetics
Male
Medical sciences
Middle Aged
Myocardial Infarction - blood
Pharmacology. Drug treatments
Plasminogen - metabolism
Plasminogen Activators - blood
Radioimmunoassay
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Summary:This study was performed to characterize selected pharmacologic properties and effects on the fibrinolytic system of tissue-type plasminogen activator synthesized by recombinant DNA technology (rt-PA) in 12 patients treated for coronary thrombosis. rt-PA was infused parenterally (by the intracoronary route in four patients and intravenously in eight) in doses of 8.3, 12.5, or 16.7 micrograms/kg/min for 30 to 60 min, yielding a total dosage of 20 to 40 mg/patient. The drug induced coronary thrombolysis in 10 of the 12 patients treated (83%), including six of the eight given rt-PA intravenously. No bleeding complications were encountered. Serial blood samples were obtained before, during, and after infusion of rt-PA and analyzed for t-PA antigen (i.e., immunoassayable rt-PA protein), functional fibrinolytic activity attributable to rt-PA, fibrinogen, plasminogen, alpha 2-antiplasmin, fibrinogen degradation products, prothrombin time, activated partial thromboplastin time, and protamine-corrected thrombin time. Pretreatment plasma t-PA antigen levels averaged 16.5 +/- 5(SD) ng/ml. Peak plasma values were generally proportional to dose, averaging 3330 +/- 1201 ng/ml. Approximately 90% of peak level was reached in 30 min, with a plateau at peak reached within 40 min. Functional t-PA activity increased monotonically in a comparable fashion. Curves for disappearance of both t-PA antigen and functional activity from plasma were monoexponential for at least two half-lives (r = .99 for both) and were concordant. The observed half-lives were similar, averaging 8.3 and 9.1 min, respectively.
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.71.1.110