Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent
Chow, Diana S-L
Teng, Yang Angela
Toups, Elizabeth G
Harrop, James S
Schmitt, Karl M
Johnson, Michele M
Guest, James D
Shaffrey, Christopher I
Frankowski, Ralph F
Fehlings, Michael G
Grossman, Robert G
JournalJournal of Clinical Pharmacology
MetadataShow full item record
AbstractRiluzole, 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. © 2021 The Authors..
Rights/Terms© 2021 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/16231
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