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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
1   The Abteilungen.III and IV, Medizinische Klinik und Poliklinik der Universität Ulm, FRG
,
P Tanswell
2   Dr. Karl Thomae GmbH, Biberach, FRG
,
D Ellbrück
1   The Abteilungen.III and IV, Medizinische Klinik und Poliklinik der Universität Ulm, FRG
,
W Haerer
1   The Abteilungen.III and IV, Medizinische Klinik und Poliklinik der Universität Ulm, FRG
,
A Schmidt
1   The Abteilungen.III and IV, Medizinische Klinik und Poliklinik der Universität Ulm, FRG
› Author Affiliations
Further Information

Publication History

Received 30 September 1988

Accepted after revision 03 March 1989

Publication Date:
24 July 2018 (online)

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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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