Safety and efficacy of 0.6 mg/kg rt-PA: optimum rt-PA dose revisited.

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.