@article{f37d616e0c5245c481b1151cd69ae3a4,
title = "Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent",
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.",
keywords = "pharmacokinetics, population modeling, riluzole, spinal cord injury",
author = "Ashley Nguyen and Chow, {Diana S.L.} and Lei Wu and Yang Teng and Mahua Sarkar and Toups, {Elizabeth G.} and Harrop, {James S.} and Schmitt, {Karl M.} and Johnson, {Michele M.} and Guest, {James D.} and Bizhan Aarabi and Shaffrey, {Christopher I.} and Maxwell Boakye and Frankowski, {Ralph F.} and Fehlings, {Michael G.} and Grossman, {Robert G.}",
note = "Funding Information: The concentration‐time data used for analysis were collected from 2 clinical trials, both of which received ethical institutional review board approval from the individual participating institutions. Informed consent was obtained from all patients. The phase 1 clinical trial investigating the safety and pharmacokinetics of riluzole was completed in 2011 (ClinicalTrials.gov Identifier: NCT00876889). RISCIS (ClinicalTrials.gov Identifier: NCT01597518) is presently an ongoing phase 2/3 multicenter randomized, placebo‐controlled, double‐blind trial to evaluate efficacy and safety of riluzole in the treatment of patients with acute SCI. The sites funded by the Department of Defense received Human Research Protection Office approval. The protocols that followed were in compliance with Good Clinical Practices. Funding Information: This study was supported by US ARMY MEDICAL RESEARCH ACQUISITION ACTIVITY under Contract No. W81XWH‐16‐C‐0031. Publisher Copyright: {\textcopyright} 2021 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology",
year = "2021",
month = sep,
doi = "10.1002/jcph.1876",
language = "English (US)",
volume = "61",
pages = "1232--1242",
journal = "Journal of Clinical Pharmacology",
issn = "0091-2700",
publisher = "SAGE Publications Inc.",
number = "9",
}