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 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.
Groeneveld
G J
GJ
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands. g.j.groeneveld@umcutrecht.nl
van Kan
H J M
HJ
Lie-A-Huen
L
L
Guchelaar
H-J
HJ
van den Berg
L H
LH
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D019540:Area Under Curve; D001499:Bayes Theorem; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000097:blood / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D019782:Riluzole / Q000097:blood* / Q000627:therapeutic use*
D018691:Excitatory Amino Acid Antagonists; D019782:Riluzole