scholarly journals Effect of intravenous administration of tissue-type plasminogen activator (AK-124) in acute myocardial infarction and changes in blood coagulation and fibrinolytic activity by the drug.

1987 ◽  
Vol 18 (6) ◽  
pp. 609-614
Author(s):  
Takashi HONDA ◽  
Masahiko AOSAKI ◽  
Tohru TANAKA ◽  
Tatsurou UCHIDA ◽  
Yoshifumi HORIKAWA ◽  
...  
1987 ◽  
Author(s):  
T Honda ◽  
M Aosaki ◽  
T Tanaka ◽  
M Aosaki ◽  
T Uchida ◽  
...  

We administered a tissue-type plasminogen activator (t-PA) intravenously to 10 patients with acute myocardial infarction (AMI), within 6 hours after the onset of symptoms, and then examined the state of reperfusion by coronary arterio graphy (CAG), and observed changes in blood coagulation and fibrinolytic activity to evaluate the drug effects. AK-124 (produced by Asahi Chemical Industry and Kowa Co., Ltd.in collaboration), a t-PA produced the by tissue cultureof normal human lung cells, was given in a dosage of48,000_576,000 A.K. units by intravenous infusionover 30_45 minutes. In 7 patients who received t-PA, areflow or improved flow was detected on CAG. In t-PAtreated patients, euglobulin lysis activity clearly increased, euglobulin lysis time clearly shortened, and D-dimer increased. After t-PA treatment, the levels of circulating fibrinogen and a2-plasmin inhibitor decreased by an average of 12%, and 14% of base-line values respectively, but plasminogen showed no detectable change. A hematoma at the site of the catheter insertion was observed in one patient. These observations suggest that t-PA has a higher specificity for fibrin bound plasminogen than for plasma plasminogen, and produces coronary thrombolysis without causing systemic fibrinolysis, at least with the above dosage.


1989 ◽  
Vol 61 (03) ◽  
pp. 497-501 ◽  
Author(s):  
E Seifried ◽  
P Tanswell ◽  
D Ellbrück ◽  
W Haerer ◽  
A Schmidt

SummaryPharmacokinetics 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.


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