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

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 variabili...

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Bibliographic Details
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
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Summary: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
ISSN:0009-9236
1532-6535
DOI:10.1038/sj.clpt.6100382