Pharmacokinetics, Bioavailability, and Swallowing Safety With Riluzole Oral Film

Abstract

Dysphagia is highly prevalent in patients with amyotrophic lateral sclerosis (ALS). Riluzole is a US Food and Drug Administration-approved treatment for ALS. Riluzole oral film (ROF; Exservan TM ) contains riluzole in a polymer-based film matrix. The ROF is administered by placing on the tongue, where it dissolves and the drug is ingested with the saliva. Two clinical trials assessed the safety and tolerability of the ROF. Bioavailability and pharmacokinetics (PK) were evaluated in an open-label, randomized, single-dose, replicate crossover study of 50 mg of ROF and riluzole 50-mg tablets in 32 healthy volunteers. The second study was a videofluoroscopic swallowing examination conducted with nine patients with ALS before and after receiving a single dose of 50 mg of ROF. The primary outcome was change on penetration-aspiration scale (PAS) scores from pre-to post-dose. Overall, the PK parameters for ROF and riluzole tablets were comparable between treatments and administrations when administered under fasting conditions. Administration of ROF with food resulted in a 15% reduction in area under the curve and a 45% reduction in maximum serum concentration. A total of 44 treatment-emergent adverse events (AEs) were reported in the study; all were mild in severity. No serious AEs were observed and no subjects discontinued due to AEs. In the swallowing study, very little numerical or categorical change was observed following the dose of ROF. No evidence of deterioration of swallowing function was observed post-dose. The ROF was bioequivalent to riluzole tablets, was well tolerated, and had no detrimental effect on swallowing.

Pharmacokinetics and bioequivalence study of montelukast sodium oral soluble film and chewable tablet in healthy Chinese volunteers: randomized trials under fasting and fed conditions

“…Moreover, it can be easily applied by different patients as well as those who cannot easily access water (8,9). Several studies have confirmed the bioequivalence between OSF and the reference formulations (e.g., sildenafil, clobazam, riluzole, and midazolam) (10)(11)(12)(13).…”

Development of a robust UPLC-MS/MS method for the quantification of riluzole in human plasma and its application in pharmacokinetics

“…In addition, as the disease progresses, swallowing difficulties may gradually appear in ALS patients, resulting in an inability to take oral riluzole tablets. Therefore, in recent years, researchers have devoted themselves to the development of new dosage forms of riluzole, such as suspension and oral films ( Wymer et al, 2023 ). The simple method was established for the determination of riluzole concentration, which was convenient for other groups to refer to, and can be applied in the study of pharmacokinetics and bioavailability of new forms of riluzole.…”

“…*When configuring whole blood stable QC samples, assuming that riluzole is not distributed in blood cells, the volume of plasma centrifuged is about half of the volume of whole blood, so the configured final concentrations of whole blood QC samples were 7.5, 30, and 300 ng/mL. Frontiers in Pharmacology frontiersin.org devoted themselves to the development of new dosage forms of riluzole, such as suspension and oral films (Wymer et al, 2023). The simple method was established for the determination of riluzole concentration, which was convenient for other groups to refer to, and can be applied in the study of pharmacokinetics and bioavailability of new forms of riluzole.…”

Current State and Future Directions in the Therapy of ALS

“…The Riluzole drug was first developed as an oral tablet of 50 mg taken twice a day but given the fact that many ALS patients are struggling with dysphagia, the development of a bioequivalent oral suspension of Riluzole (5 mg/mL) was essential [34,35]. Furthermore, recently, an oral-film formulation form of Riluzole has been developed that poses another option to simplify administration and ensure the continuation of medical treatment [36,37].…”