Human recombinant tissue-plasminogen activator (alteplase): why not use the 'human' dose for stroke studies in rats?
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.
Haelewyn
Benoît
B
NNOXe Pharmaceuticals, Quebec City, Quebec, Canada.
Risso
Jean-Jacques
JJ
Abraini
Jacques H
JH
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator