Riluzole serum concentrations in patients with ALS

Abstract

Riluzole exerts a dose-dependent effect on survival of patients with ALS and, although serum levels show a high interindividual variability, is usually prescribed in a fixed dose. In this study, riluzole serum levels and area under the curve per kilogram of body weight (AUC/kg) of 169 patients with ALS showed a high interindividual variability. Patients with high serum levels and AUC/kg more often had diarrhea but less often had fasciculations and muscle stiffness. It may therefore be advantageous to raise the riluzole dose in patients with low riluzole serum concentrations without the risk of serious side effects.

Firing pattern of fasciculations in ALS

“…Intriguingly, riluzole has been found to block these persistent sodium currents, 47 but has at the same time a dose-dependent suppressive effect on fasciculations in patients with ALS. 48 This could indicate that fasciculations in ALS may not be associated with persistent inward currents, but with abnormal phasic input to the spinal motor neuron. Such abnormal impulses form a hyperexcitable cortex should reach a number of lowthreshold motor neurons in the spinal cord.…”

Review of the Use of the Glutamate Antagonist Riluzole in Psychiatric Disorders and a Description of Recent Use in Childhood Obsessive-Compulsive Disorder

“…The one clinical study that attempted to correlate adverse effects and benefits with serum levels found that diarrhea was more common at higher doses, but fasciculations were less common (possibly implying a neuromuscular benefit) (Groeneveld et al 2003). No relationship was found between riluzole serum levels and survival in one study .…”

The Anticonvulsants Lamotrigine, Riluzole, and Valproate Differentially Regulate AMPA Receptor Membrane Localization: Relationship to Clinical Effects in Mood Disorders

“…These cultures yielded virtually pure neurons (Supplementary Figure 2). Doses of drugs chosen were based on their therapeutic plasma concentrations clinically (Groeneveld et al, 2003;Hirsch et al, 2004;Zarate et al, 2005). Thus, concentrations of lamotrigine (20 mM), riluzole (2.0 mM), and valproate (1.0 mM) were chosen for our studies.…”