STEADY-STATE PHARMACOKINETICS OF IDEBENONE IN HEALTHY-VOLUNTEERS

An open study was conducted with 12 healthy male Caucasian volunteers to determine the single dose and steady-state pharmacokinetics in plasma after a total daily dose of 90 mg of idebenone administered as 45 mg twice daily for 10 consecutive days. In the dose regimen investigated, multiple daily doses of 90 mg of idebenone were well tolerated by healthy male volunteers and were not associated with any clinically relevant changes in ECG or clinical laboratory parameters. The results of the physical examinations after study termination revealed normal findings in all volunteers. To evaluate the single dose and steady-state pharmacokinetic profile, blood samples were collected at predetermined time points during the study. In those subjects examined, generally good systemic exposure with rapid absorption of idebenone was obtained throughout the entire dosing period. Exposures to idebenone and its metabolites after both single and repeated oral doses of idebenone were comparable in magnitude. Further, the exposures attained were generally consistent with those observed in a previous study after 30 mg three times daily. All pharmacokinetic assessments were associated with a low to moderate degree of inter-subject variability.