Purpose: Edaravone is a free-radical scavenger. Edaravone 30 mg IV has been approved for use in the treatment of acute ischemic stroke in Japan and China, and for amyotrophic lateral sclerosis in Japan and the United States. Considering the inconvenience of IV infusion in clinical practice, an oral tablet formulation of edaravone was developed but failed in 2011 due to poor bioavailability. More recently, a sublingual (SL) tablet formulation of edaravone 30 mg was developed by a Good Manufacturing Practices-compliant manufacturer in China. This study explored the bioavailability of the SL tablet of edaravone and aimed to provide evidence to support decision making in future clinical development. Methods: This 2-way crossover study was conducted in 10 healthy male volunteers. Eligible subjects were randomized, in a 1:1 ratio, to 1 of 2 dosing sequences: (1) SL edaravone 30 mg, followed by edaravone 30 mg IV infusion given over 30 minutes; or (2) edaravone 30 mg IV infusion given over 30 minutes, followed by SL edaravone 30 mg. The washout period between the 2 dosing periods was at least 24 hours. Serial blood samples were collected in each dosing period. The bioavailability of the SL tablet was assessed using bioavailability analysis. Tolerability was evaluated throughout the study. Findings: The plasma concentration-time profile of the SL tablet was similar to that with the IV infusion. A mean (SD) C-max of 2030.2 (517.2) ng/mL was reached within a median T-max of 0.875 hour, which was statistically significantly longer than the median Tmax with IV administration (0.5 hour). The C-max with SL administration corresponded to 83.92% (90% CI, 73.22%-96.18%) of the C-max with the start of IV infusion (2354.0 [336.6] ng/mL). The mean AUC(0-t) with SL dosing was 5420.07 (1429.75) h.ng/mL, which corresponded to 91.94% (90% CI, 86.81%-97.39%) of the AUC(0-t) with IV administration (5824.42 [1338.48] h.ng/mL). Two cases of adverse events were reported during the study; both were considered by the investigator to have been possibly not related to the study treatment. (C) 2018 Elsevier Inc. All rights reserved.