Longitudinal impacts of acute spinal cord injury on clinical pharmacokinetics of riluzole, a potential neuroprotective agent.

Riluzole, a benzothiazole sodium channel blocker that received FDA approval to attenuate neurodegeneration in amyotrophic lateral sclerosis (ALS) in 1995, was found to be safe and potentially efficacious in a spinal cord injury (SCI) population as evident in a Phase I clinical trial. The acute and progressive nature of traumatic SCI and the complexity of secondary injury processes can alter the pharmacokinetics of therapeutics. A one-compartment with first-order elimination population pharmacokinetic model for riluzole incorporating time-dependent clearance and volume of distribution was developed from combined data of the Phase I and the ongoing Phase II/III trials. This change in therapeutic exposure may lead to a biased estimate of the exposure-response relationship when evaluating therapeutic effects. With the developed model, a rational, optimal dosing scheme can be designed with time-dependent modification that preserves the required therapeutic exposure of riluzole. This article is protected by copyright. All rights reserved.