Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent

Ashley Nguyen, Diana S.L. Chow, Lei Wu, Yang Teng, Mahua Sarkar, Elizabeth G. Toups, James S. Harrop, Karl M. Schmitt, Michele M. Johnson, James D. Guest, Bizhan Aarabi, Christopher I. Shaffrey, Maxwell Boakye, Ralph F. Frankowski, Michael G. Fehlings, Robert G. Grossman

Research output: Contribution to journalArticlepeer-review

Abstract

Riluzole, a benzothiazole sodium channel blocker that received US Food and Drug Administration approval to attenuate neurodegeneration in amyotrophic lateral sclerosis 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 1-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 1 and the ongoing phase 2/3 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.

Original languageEnglish (US)
Pages (from-to)1232-1242
Number of pages11
JournalJournal of Clinical Pharmacology
Volume61
Issue number9
DOIs
StatePublished - Sep 2021

Keywords

  • pharmacokinetics
  • population modeling
  • riluzole
  • spinal cord injury

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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