WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Spinal muscular atrophy (SMA) is a neuromuscular disorder of childhood.

• Riluzole is an anti-excitatory agent recommended for the treatment of amyotrophic lateral sclerosis (ALS).

• Riluzole pharmacokinetics are well documented in patients with ALS.

WHAT THIS STUDY ADDS

• Riluzole pharmacokinetics have never documented in patients with SMA.

• This study showed that the administration of 50 mg riluzole once a day to patients with SMA leads to total riluzole daily exposure comparable with that obtained after the administration of 50 mg twice a day in healthy volunteers or ALS patients.

AIMS

The objective of the present study was to assess the pharmacokinetics of riluzole in patients with spinal muscular atrophy (SMA).

METHODS

Fourteen patients were enrolled in an open-label, nonrandomized and repeat-dose pharmacokinetic study. All participants were assigned to receive 50 mg riluzole orally for 5 days. Riluzole plasma concentrations were determined from samples obtained at day 5.

RESULTS

The pharmacokinetic analysis demonstrated that a dose of 50 mg once a day was sufficient to obtain a daily total exposure [AUC(0,24 h) = 2257 ng ml^-1 h] which was comparable with results obtained in adult healthy volunteers or ALS patients in whom a dose of 50 mg twice a day is recommended. The pharmacokinetic simulation demonstrated that the administration of 50 mg twice a day could result in higher concentrations, hence reduced safety margin.

CONCLUSION

The dose of 50 mg once a day was chosen for the clinical trial evaluating the efficacy of riluzole in SMA patients.