An Association Study of Riluzole Serum Concentration and Survival and Disease Progression in Patients With ALS

• Published in: Clinical pharmacology and therapeutics 2008-05, Vol.83 (5), p.718-722
• Main Authors: Groeneveld, GJ, Kan, HJM, Lie‐A‐Huen, L, Guchelaar, H‐J, Berg, LH
• Format: Article
• Language: English
• Subjects: Adult; Aged; Amyotrophic Lateral Sclerosis - blood; Amyotrophic Lateral Sclerosis - drug therapy; Amyotrophic Lateral Sclerosis - pathology; Area Under Curve; Bayes Theorem; Biological and medical sciences; Disease Progression; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists - blood; Excitatory Amino Acid Antagonists - therapeutic use; Female; Humans; Linear Models; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Proportional Hazards Models; Riluzole - blood; Riluzole - therapeutic use
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1038/sj.clpt.6100382

Patients with amyotrophic lateral sclerosis (ALS) who are treated with the antiglutamatergic drug riluzole receive a fixed‐dose regimen of 50 mg b.i.d. The drug has been shown to increase tracheostomy‐free survival by 3–6 months. The pharmacokinetics of riluzole show a high interindividual variability. Riluzole serum concentrations are associated with side effects and ALS symptoms, but the effect of the actual blood level of riluzole on disease progression and survival is unknown. We measured trough and peak serum concentrations of riluzole in 160 patients with ALS, and estimated the area under the curve for one dosage interval (AUCi) using a Bayesian method. We then determined the association between riluzole AUCi and survival over a 5‐year period, and between riluzole AUCi and disease progression, defined by the rates of decline of arm strength and vital lung capacity. No significant association was found between riluzole AUCi and survival or disease progression. Clinical Pharmacology & Therapeutics (2008); 83, 5, 718–722. doi:10.1038/sj.clpt.6100382