The neuroprotective agent edaravone is an intravenous treatment for amyotrophic lateral sclerosis. As intravenous administration burdens patients, orally administered treatments are needed. This phase 1, open‐label, single‐dose crossover study in 42 healthy adults evaluated bioequivalence of a 105‐mg edaravone oral suspension and intravenous edaravone (60 mg/60 min). The evaluation was whether the 90% confidence intervals (CIs) for the ratio of the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from time 0 to the last quantifiable time point and to infinity of unchanged edaravone were between the bioequivalence limit of 0.80 and 1.25. Metabolic profiles and elimination pathways were also compared between the 2 routes. Geometric mean ratios and 90%CIs of area under the plasma concentration–time curve from time 0 to the last quantifiable time point and to infinity for unchanged edaravone satisfied bioequivalence limits. The geometric mean ratio and its lower limit of 90%CI of Cmax of the 105‐mg oral suspension compared with 60‐mg intravenous formulations for unchanged edaravone fell within bioequivalence limits. Both formulations showed triphasic plasma concentration–time profiles of unchanged edaravone after reaching Cmax. Plasma concentrations of edaravone inactive metabolites after oral administration were higher than with intravenous administration. Edaravone in both routes underwent urinary excretion, mainly as the glucuronide conjugate and, to a lesser extent, as the sulfate conjugate. Urinary excretion of unchanged edaravone was low, and urinary relative composition ratios of unchanged edaravone and metabolites were similar for both formulations. These findings showed equivalent exposure of the 105‐mg oral suspension of edaravone to the 60‐mg intravenous formulation, supporting further investigation of the oral suspension for treating amyotrophic lateral sclerosis.

Intravenous edaravone is used to treat patients with amyotrophic lateral sclerosis. This randomized, open-label, two-way crossover, single-dose phase 1 study compared the relative bioavailability of a newly developed edaravone oral suspension when administered orally and via a nasogastric tube (NGT) as a model of percutaneous endoscopic gastrostomy tube administration in healthy adult subjects. Thirty-six subjects were randomly assigned to one of two groups, with 18 per group. Blood was collected pre-and post-dose for pharmacokinetic assessments; safety was evaluated. Plasma concentration-time profiles of unchanged edaravone were similar between administration routes. Comparative bioavailability analysis revealed that geometric least squares mean ratios (NGT/oral) for maximum plasma concentration and area under the plasma concentration-time curve from time zero to infinity of unchanged edaravone were 1.052 and 0.981, respectively. No serious adverse events or adverse drug reactions were reported. These results suggest that oral edaravone suspension can be administered directly to the stomach without dose adjustment via feeding tubes; both oral and NGT administration are well tolerated.

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