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Single‐ and Multiple‐Dose Pharmacokinetics of Riluzole in White Subjects
Author(s) -
Liboux Aimé Le,
Lefebvre Patricia,
Roux Yvonne Le,
Truffinet Philippe,
Aubeneau Michel,
Kirkesseli Stéphane,
Montay Guy
Publication year - 1997
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1997.tb05630.x
Subject(s) - riluzole , pharmacokinetics , cmax , bioavailability , pharmacology , oral administration , area under the curve , absorption (acoustics) , medicine , half life , dose–response relationship , chemistry , amyotrophic lateral sclerosis , physics , disease , acoustics
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 (C max ) and area under the concentration—time curve (AUC) values were linearly related to dose for the range studied. 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 intraindividual variability in bioavailability was seen. A high‐fat meal significantly 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 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.