SINGLE-DOSE AND MULTIPLE-DOSE PHARMACOKINETICS OF RILUZOLE IN WHITE SUBJECTS

Riluzole is a novel neuroprotective agent that has been developed for the treatment of amyotrophic lateral sclerosis. A series of studies wa s undertaken to establish its pharmacokinetics on single-and multiple- dose administration in young white male volunteers. The mean absolute oral bioavailability of riluzole (50-mg tablet) was approximately 60%. Maximum plasma concentration (C-max) and area under the concentration time curve (AUC) values were linearly related to dose for the range s tudied. C-max occurred at 1.0 hour to 1.5 hours after administration. Plasma elimination half-life appeared to be independent of dose. After repeated administration of 100 mg riluzole for 10 days, some intraind ividual variability in bioavailability was seen. A high-fat meal signi ficantly reduced the rate (t(max) = 2 hours compared with 0.8 hours; C -max = 216 ng.mL(-1) compared to 387 ng.mL(-1)) and extent of absorpti on (AUC = 1,047 ng.hr.mL(-1) versus 1,269 ng.hr.ml(-1)). With multiple -dose administration, riluzole showed dose-related absorption, althoug h the terminal plasma half-life was prolonged slightly. Steady-state p lasma concentrations were achieved within 5 days. Steady-state trough plasma concentrations were significantly higher with a 75-mg dose twic e daily than with a 50-mg dose three times daily, although AUC values did not differ.