PMID- 7843689
OWN - NLM
STAT- MEDLINE
DCOM- 19950308
LR  - 20161123
IS  - 0340-9937 (Print)
IS  - 0340-9937 (Linking)
VI  - 19
IP  - 6
DP  - 1994 Dec
TI  - [Pro-urokinase for infarct therapy].
PG  - 326-35
AB  - The development of new thrombolytic agents is concentrating on substances which 
      are more effective and more fibrin specific than streptokinase. Prourokinase is a 
      single chain urokinase-type plasminogen activator (scu-PA). The recombinant 
      unglycosylated prourokinase (saruplase) is synthesized in transformed E coli 
      bacteria. The dominant half life is 9 minutes. With the standard dosage regimen 
      about 28% of saruplase is converted into two chain urokinase-type plasminogen 
      activator (tcu-PA), which is rapidly inactivated by plasma inhibitors whereas 
      saruplase is not. Saruplase is fibrin-specific since it predominantly activates 
      plasminogen bound to fibrin. Even without measurable conversion to tcu-PA, 
      saruplase appears able to activate fibrin. The fibrin specific action is dose 
      dependent and correlates inversely with the rate of saruplase converted to 
      tcu-PA. Dose finding studies have shown that a 20 mg bolus followed by 60 mg 
      given intravenously over 60 minutes is an effective thrombolytic regimen. In the 
      PASS-study 1,698 patients were treated with saruplase. The results of the 
      PASS-study (Table 1) confirmed the efficacy and safety of the 20/60 mg dosage. 
      This standard dosage has been compared with streptokinase, urokinase and 
      alteplase in randomized multicenter-studies. The systemic fibrinolytic activity 
      is less in comparison to streptokinase but higher than the systemic fibrinolytic 
      activity of alteplase. In the PRIM1-study the early patency (60: minutes) was 
      significantly higher with saruplase in comparison to streptokinase (Figure 1). 
      Patency after 90 minutes and 24 to 36 hours did not differ significantly between 
      both substances. Bleeding complications were less frequent with saruplase. 
      Urokinase was compared with saruplase in the SUTA-MI-study. The patency rates 
      (TIMI-flow 2 and 3) at 24 to 72 hours were similar in both groups (saruplase 
      75.4%, urokinase 74.2%). Hospital mortality was higher in the urokinase group 
      (8.1% vs 4.4%), but this difference was not significant. The efficacy and safety 
      of saruplase (80 mg, 1 hour) was compared with alteplase (100 mg, 3 hours) in the 
      SESAM-study. There was a non significant trend towards earlier patency with 
      saruplase at 45 min (Figure 2). Complication rates and hospital mortality were 
      similar in both groups. The importance of heparin comedication was investigated 
      in the LIMITS-study.(ABSTRACT TRUNCATED AT 400 WORDS)
FAU - Spiecker, M
AU  - Spiecker M
AD  - II. Medizinische Klinik und Poliklinik, Johannes-Gutenberg-Universitat Mainz.
FAU - Meyer, J
AU  - Meyer J
LA  - ger
PT  - Comparative Study
PT  - Journal Article
PT  - Review
TT  - Prourokinase fur die Infarkttherapie.
PL  - Germany
TA  - Herz
JT  - Herz
JID - 7801231
RN  - 0 (Anticoagulants)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - U5NH2JV64T (saruplase)
SB  - IM
MH  - Anticoagulants/administration & dosage/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Therapy, Combination
MH  - Hospital Mortality
MH  - Humans
MH  - Myocardial Infarction/*drug therapy/mortality
MH  - Randomized Controlled Trials as Topic
MH  - Recombinant Proteins/administration & dosage/adverse effects
MH  - Thrombolytic Therapy/*methods
MH  - Tissue Plasminogen Activator/administration & dosage/adverse effects
MH  - Urokinase-Type Plasminogen Activator/*administration & dosage/adverse effects
RF  - 55
EDAT- 1994/12/01 00:00
MHDA- 1994/12/01 00:01
CRDT- 1994/12/01 00:00
PHST- 1994/12/01 00:00 [pubmed]
PHST- 1994/12/01 00:01 [medline]
PHST- 1994/12/01 00:00 [entrez]
PST - ppublish
SO  - Herz. 1994 Dec;19(6):326-35.