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.
Protein binding is 96%, mainly to albumin and lipoproteins. Penetrates brain readily.
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.
Eliminated in urine (more than 85% glucuronide metabolites; 2% unchanged) and small amount in feces. T ½ is 12 h (after multiple dosing).
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.
Age-related decreased renal function will give higher plasma levels of riluzole and metabolites.
CYP1A2 activity has been reported to be lower in women and may result in higher blood concentrations and metabolites.
Clearance of drug in Japanese subjects was found to be 50% lower; may possess a lower capacity (oxidative or conjugative) for metabolizing riluzole.
Induces CYP1A2 and will eliminate riluzole faster; no information on need to adjust dose in these patients.