SAFETY AND PHARMACOKINETICS OF THE NEUROPROTECTIVE DRUG LUBELUZOLE INPATIENTS WITH ISCHEMIC STROKE

A total of 22 patients with acute ischemic stroke participated in two randomized, single-masked, placebo-controlled studies that evaluated t he safety and pharmacokinetics of single escalating intravenous doses of lubeluzole. The first dose of study medication in all patients was given within 6 hours of the first sign of stroke onset. In the first s tudy, 6 patients received a single 1-hour intravenous infusion of 5 mg of lubeluzole; 4 of these patients received an additional 10-mg dose 3 to 4 days later. Two additional patients received placebo. In the se cund study, 4 patients received a single 1-hour infusion of 10 mg of l ubeluzole, and 2 patients received placebo. After a safety evaluation of the second study, 6 additional patients received 15 mg of lubeluzol e, and 2 other patients received placebo. Lubeluzole had no clinically relevant effects on any cardiovascular variable compared with placebo . The majority of adverse experiences were mild to moderate and resolv ed during treatment. No unexpected electroencephalogram abnormalities were observed, and no evidence of epileptiform discharges was found in any of the patients. At the end of the infusion, plasma lubeluzole co ncentrations decayed biphasically, with mean distribution half-lives o f 46.3 to 101.0 minutes and mean terminal half-lives of 20.8 to 27.7 h ours. Comparisons of the dose-normalized values of the individual plas ma concentrations at the end of the infusion and the total area under the curve from time 0 to infinity suggested that lubeluzole exhibited linear kinetics over the dose range evaluated in patients with ischemi c stroke. In the small number of patients studied, lubeluzole's favora ble safety profile was demonstrated by the lack of clinically relevant effects on cardiovascular variables and by neurologic examination and clinical laboratory findings.