title: Single- and multiple-dose pharmacokinetics of riluzole in white subjects.
abstract: Riluzole is a novel neuroprotective agent that has been developed for the treatment of amyotrophic lateral sclerosis. A series of studies was 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 (Cmax) and area under the concentration-time curve (AUC) values were linearly related to dose for the range studied. Cmax 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 intraindividual variability in bioavailability was seen. A high-fat meal significantly reduced the rate (tmax = 2 hours compared with 0.8 hours; Cmax = 216 ng.mL-1 compared to 387 ng.mL-1) and extent of absorption (AUC = 1,047 ng.hr.mL-1 versus 1,269 ng.hr.mL-1). With multiple-dose administration, riluzole showed dose-related absorption, although the terminal plasma half-life was prolonged slightly. Steady-state plasma concentrations were achieved within 5 days. Steady-state trough plasma concentrations were significantly higher with a 75-mg dose twice daily than with a 50-mg dose three times daily, although AUC values did not differ.
authors.affiliation: Rhone-Poulenc Rorer Recherche-Développement, Antony, France.
authors.forename: A
authors.initials: A
authors.lastname: Le Liboux
authors.forename: P
authors.initials: P
authors.lastname: Lefebvre
authors.forename: Y
authors.initials: Y
authors.lastname: Le Roux
authors.forename: P
authors.initials: P
authors.lastname: Truffinet
authors.forename: M
authors.initials: M
authors.lastname: Aubeneau
authors.forename: S
authors.initials: S
authors.lastname: Kirkesseli
authors.forename: G
authors.initials: G
authors.lastname: Montay
mesh_terms: D000293:Adolescent; D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D019782:Riluzole / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D018691:Excitatory Amino Acid Antagonists; D019782:Riluzole