This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tiefenbrunn, A. J. Articles by Sobel, B. E. Search for Related Content PubMed PubMed Citation Articles by Tiefenbrunn, A. J. Articles by Sobel, B. E. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Heart Attack

Circulation, Vol 71, 110-116, Copyright © 1985 by American Heart Association

ARTICLES

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

AJ Tiefenbrunn, AK Robinson, PB Kurnik, PA Ludbrook and BE Sobel

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.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				W. D. Irvine, M. W. Johnson, E. Hernandez, and K. R. Olsen Retinal Toxicity of Human Tissue Plasminogen Activator in Vitrectomized Rabbit Eyes Arch Ophthalmol, May 1, 1991; 109(5): 718 - 722. [Abstract] [PDF]

				M. W. Johnson, K. R. Olsen, E. Hernandez, W. D. Irvine, and R. N. Johnson Retinal Toxicity of Recombinant Tissue Plasminogen Activator in the Rabbit Arch Ophthalmol, February 1, 1990; 108(2): 259 - 263. [Abstract] [PDF]

				M. A. Sloan Thrombolysis and Stroke: Past and Future Arch Neurol, July 1, 1987; 44(7): 748 - 768. [Abstract] [PDF]

				P. L. Zwerner and J. M. Gore Analytic Review: Thrombolytic Therapy in Acute Myocardial Infarction J Intensive Care Med, December 1, 1986; 1(6): 302 - 318. [Abstract] [PDF]

				A. S. Jaffe and B. E. Sobel Thrombolysis With Tissue-Type Plasminogen Activator in Acute Myocardial Infarction: Potentials and Pitfalls JAMA, January 10, 1986; 255(2): 237 - 239. [Abstract] [PDF]

				E. J. TOPOL, W. R. BELL, and M. L. WEISFELDT Coronary Thrombolysis with Recombinant Tissue-Type Plasminogen Activator: A Hematologic and Pharmacologic Study Ann Intern Med, December 1, 1985; 103(6_Part_1): 837 - 843. [Abstract] [PDF]

				C Bode, G. Matsueda, K. Hui, and E Haber Antibody-directed urokinase: a specific fibrinolytic agent Science, August 23, 1985; 229(4715): 765 - 767. [Abstract] [PDF]