title: Inter- and intraindividual variability of riluzole serum concentrations in patients with ALS.
abstract: All patients with amyotrophic lateral sclerosis (ALS) are treated with the same dose of riluzole: 50 mg twice daily. Reasonably large interindividual differences in clearance of the drug have been reported. The relatively small group of patients with high blood concentrations of riluzole has probably primarily influenced the efficacy and the incidence of side-effects in the previously conducted clinical trials with riluzole. Individual dosing of the drug may, in the case of large interindividual differences in serum concentrations of the drug, be necessary in the future. Exact data concerning the plasma and serum concentrations of riluzole in patients with ALS, after standardized intake of the drug, diet and blood sampling are unknown so far. In this study, inter- and intraindividual variability of serum and plasma levels of riluzole in 21 patients with "probable" or "definite" ALS were determined. The interindividual variability of peak serum levels (coefficient of variation=74%) was significantly larger than intraindividual variability (p<0.001). Serum levels were not correlated with age or smoking status. The determination of a correlation between riluzole serum concentrations and survival of patients with ALS will be the aim of further studies.
authors.affiliation: Neuromuscular Center Utrecht, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands. g.j.groeneveld@neuro.azu.nl
authors.forename: G J
authors.initials: GJ
authors.lastname: Groeneveld
authors.forename: H J
authors.initials: HJ
authors.lastname: van Kan
authors.forename: J S
authors.initials: JS
authors.lastname: Toraño
authors.forename: J H
authors.initials: JH
authors.lastname: Veldink
authors.forename: H J
authors.initials: HJ
authors.lastname: Guchelaar
authors.forename: J H
authors.initials: JH
authors.lastname: Wokke
authors.forename: L H
authors.initials: LH
authors.lastname: van den Berg
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000188:drug therapy; D000704:Analysis of Variance; D005260:Female; D014644:Genetic Variation; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015203:Reproducibility of Results; D019782:Riluzole / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012907:Smoking
chemical_list: D018696:Neuroprotective Agents; D019782:Riluzole