title: Safety and efficacy of 0.6 mg/kg rt-PA: optimum rt-PA dose revisited.
abstract: Although the internationally recommended dosage of alteplase, a single-chain rt-PA, is 0.9 mg/kg, 0.6 mg/kg is the only approved dosage in Japan, and it is widely used there. Duteplase is a two-chain rt-PA, and based on findings of the duteplase trials in the early 1990s, the smaller dosage of 0.6 mg/kg of alteplase was tested in the Japan Alteplase Clinical Trial (J-ACT), which indicated that the efficacy/safety profile of this dose was comparable to the 0.9 mg/kg dosage used in other countries. The Japan Alteplase Clinical Trial II (J-ACT II) further demonstrated efficacy of 0.6 mg/kg alteplase with regard to vascular outcomes in patients with middle cerebral artery (MCA) occlusion. Finally, the Japan post-Marketing Alteplase Registration Study (J-MARS) confirmed the efficacy/safety profile of 0.6 mg/kg alteplase in a clinical setting that was comparable to the dose of 0.9 mg/kg in the European counterpart, the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST). The dose of 0.6 mg/kg seems to be optimal, at least in far-east Asians, and might be extrapolated to other ethnic groups as well.
authors.affiliation: Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan. morie@med.tohoku.ac.jp
authors.forename: Etsuro
authors.initials: E
authors.lastname: Mori
mesh_terms: D044466:Asian People; D002545:Brain Ischemia / Q000188:drug therapy* / Q000208:ethnology; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan / Q000208:ethnology; D018810:Magnetic Resonance Angiography; D015201:Meta-Analysis as Topic; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; C068645:duteplase