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Absorption
Well absorbed (about 90%). Oral bioavailability is about 50%. High fat meals decrease absorption, decrease AUC about 20% and peak blood levels by about 45%. Steady state is less than 5 days.
Distribution
Protein binding is 96%, mainly to albumin and lipoproteins. Penetrates brain readily.
Metabolism
Extensively metabolized to 6 major and a number of minor metabolites via CYP-450 dependent hydroxylation and glucuronidation. CYP-450 1A2 is the main isoenzyme involved in N-hydroxylation.
Elimination
Eliminated in urine (more than 85% glucuronide metabolites; 2% unchanged) and small amount in feces. T ½ is 12 h (after multiple dosing).
Special Populations
Renal Function Impairment
Reduced clearance of riluzole and its metabolites leading to higher plasma levels.
Hepatic Function Impairment
Reduced clearance of riluzole and its metabolites, leading to higher plasma levels.
Elderly
Age-related decreased renal function will give higher plasma levels of riluzole and metabolites.
Gender
CYP1A2 activity has been reported to be lower in women and may result in higher blood concentrations and metabolites.
Race
Clearance of drug in Japanese subjects was found to be 50% lower; may possess a lower capacity (oxidative or conjugative) for metabolizing riluzole.
Smoking
Induces CYP1A2 and will eliminate riluzole faster; no information on need to adjust dose in these patients.
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