Pharmacokinetics and Haemostatic Status During Consecutive Infusions of Recom binant Tissue-Type Plasminogen Activator in Patients with Acute Myocardial Infarction

E Seifried; P Tanswell; D Ellbrück; W Haerer; A Schmidt

doi:10.1055/s-0038-1646622

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1989; 61(03): 497-501
DOI: 10.1055/s-0038-1646622

Original Article

Schattauer GmbH Stuttgart

Pharmacokinetics and Haemostatic Status During Consecutive Infusions of Recom binant Tissue-Type Plasminogen Activator in Patients with Acute Myocardial Infarction

E Seifried

¹The Abteilungen.III and IV, Medizinische Klinik und Poliklinik der Universität Ulm, FRG

,

P Tanswell

²Dr. Karl Thomae GmbH, Biberach, FRG

,

D Ellbrück

¹The Abteilungen.III and IV, Medizinische Klinik und Poliklinik der Universität Ulm, FRG

,

W Haerer

¹The Abteilungen.III and IV, Medizinische Klinik und Poliklinik der Universität Ulm, FRG

,

A Schmidt

¹The Abteilungen.III and IV, Medizinische Klinik und Poliklinik der Universität Ulm, FRG

› Institutsangaben

Abstract

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Summary

Pharmacokinetics and systemic effects of recombinant tissue type plasminogen activator (rt-PA) were determined during coronary thrombolysis in 12 acute myocardial infarction patients using a consecutive intravenous infusion regimen. Ten mg rt-PA were infused in 2 minutes resulting in a peak plasma concentration (mean ±SD) of 3310±950 ng/ml, followed by 50 mg in 1 h and 30 mg in 1.5 h yielding steady state plasma levels of. 2210±470 nglml and 930±200 ng/ml, respectively. All patients received intravenous heparin. Total clearance of rt-PA was 380±74 ml/min, t,_½α was 3.6±0.9 min and t,_½β was 16±5.4 min.

After 90 min, in plasma samples containing anti-rt-PA-IgG to inhibit in vitro effects, fibrinogen was decreased to 54%, plasminogen to 52%, α₂-antiplasmin to 25%, α₂-macroglobulin to 90% and antithrombin III to 85% of initial values. Coagulation times were prolonged and fibrin D-dimer concentrations increased from 0.40 to 2.7 μg/ml. It is concluded that pharmacokinetics of rt-PA show low interpatient variability and that its short mean residence time in plasma allows precise control of therapy. Apart from its moderate effect on the haemostatic system, rt-PA appears to lyse a fibrin pool in addition to the coronary thrombus.

Keywords

rt-PA - Myocardial infarction - Pharmacokinetics - Systemic haemostasis

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Referenzen

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