PMID- 8269200
OWN - NLM
STAT- MEDLINE
DCOM- 19940128
LR  - 20191023
IS  - 0954-6928 (Print)
IS  - 0954-6928 (Linking)
VI  - 4
IP  - 10
DP  - 1993 Oct
TI  - Coronary thrombolysis with K1K2Pu, a chimeric tissue-type and urokinase-type 
      plasminogen activator: a feasibility study in six patients with acute myocardial 
      infarction.
PG  - 929-33
AB  - BACKGROUND: K1K2Pu is a recombinant chimeric tissue-type and urokinase-type 
      plasminogen activator consisting of the two kringle domains (K1 and K2) of human 
      tissue-type plasminogen activator (t-PA) and the serine proteinase domain (Pu) of 
      single-chain urokinase-type plasminogen activator (scu-PA). In experimental 
      animal models of thrombosis, its thrombolytic potency has been shown to be five- 
      to 10-fold greater than that of its parent molecules. METHODS: The effect of a 
      bolus injection of K1K2Pu on coronary thrombolysis over 30 min was evaluated in 
      six patients with acute myocardial infarction of less than 5 h duration in whom 
      total occlusion of the infarct-related artery was confirmed using angiography. 
      RESULTS: In two patients given an intravenous bolus of 10 mg over 5 min, 
      persistent coronary artery recanalization was not observed within 30 min. In two 
      out of four patients given a second bolus of 10 mg K1K2Pu, 15 min after the 
      first, persistent coronary recanalization occurred within 30 min. The four 
      patients without recanalization within 30 min were immediately given 100 mg t-PA 
      over 90 min. In all patients the infarct-related artery was patent after 24 h, 
      and the hospital course was uneventful. The bolus injections did not produce 
      significant fibrinogen breakdown or alpha 2-antiplasmin consumption within 30 
      min. The plasma K1K2Pu level increased to 2-3 micrograms/ml after the first bolus 
      injection and to 4-5 micrograms/ml after the second. K1K2Pu disappeared from the 
      plasma with an initial half-life of 9 min and a clearance of approximately 50 
      ml/min. CONCLUSION: A bolus injection of 20 mg K1K2Pu is well tolerated and can 
      induce clot-selective coronary thrombolysis in patients with acute myocardial 
      infarction.
FAU - Van de Werf, F
AU  - Van de Werf F
AD  - Center for Molecular and Vascular Biology, University Hospitals, University of 
      Leuven, Belgium.
FAU - Lijnen, H R
AU  - Lijnen HR
FAU - Collen, D
AU  - Collen D
LA  - eng
PT  - Journal Article
PL  - England
TA  - Coron Artery Dis
JT  - Coronary artery disease
JID - 9011445
RN  - 0 (K1K2Pu)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 3.4.21.- (Plasminogen Activators)
SB  - IM
MH  - Aged
MH  - Coronary Thrombosis/complications/*drug therapy
MH  - Feasibility Studies
MH  - Female
MH  - Humans
MH  - Injections, Intravenous
MH  - Male
MH  - Middle Aged
MH  - Myocardial Infarction/complications/*drug therapy
MH  - *Plasminogen Activators
MH  - Recombinant Fusion Proteins/administration & dosage/pharmacokinetics/*therapeutic 
      use
MH  - *Thrombolytic Therapy/methods
EDAT- 1993/10/01 00:00
MHDA- 1993/10/01 00:01
CRDT- 1993/10/01 00:00
PHST- 1993/10/01 00:00 [pubmed]
PHST- 1993/10/01 00:01 [medline]
PHST- 1993/10/01 00:00 [entrez]
AID - 10.1097/00019501-199310000-00013 [doi]
PST - ppublish
SO  - Coron Artery Dis. 1993 Oct;4(10):929-33. doi: 10.1097/00019501-199310000-00013.