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J Cereb Blood Flow Metab. 2010 May;30(5):900-3. doi: 10.1038/jcbfm.2010.33. Epub 2010 Mar 10.

Human recombinant tissue-plasminogen activator (alteplase): why not use the 'human' dose for stroke studies in rats?

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  • 1NNOXe Pharmaceuticals, Quebec City, Quebec, Canada.


Since a pioneer work that has shown in vitro that the rat's fibrinolytic system is 10-fold less sensitive to recombinant tissue-plasminogen activator (rtPA) than the human system, most preclinical studies are performed with 10 instead of 0.9 mg/kg rtPA (the clinical dose in stroke patients). In this study, we compared the effects of these doses on mean time to reperfusion, reperfusion slope, brain infarct volume and edema in a rat model of thrombo-embolic stroke. Our data provide evidence that the dose of 0.9 mg/kg rtPA is as appropriate as that of 10 mg/kg for preclinical stroke studies in rodents.

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