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Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent
Author(s) -
Nguyen Ashley,
Chow Diana SL.,
Wu Lei,
Teng Yang Angela,
Sarkar Mahua,
Toups Elizabeth G.,
Harrop James S.,
Schmitt Karl M.,
Johnson Michele M.,
Guest James D.,
Aarabi Bizhan,
Shaffrey Christopher I.,
Boakye Maxwell,
Frankowski Ralph F.,
Fehlings Michael G.,
Grossman Robert G.
Publication year - 2021
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1876
Subject(s) - riluzole , medicine , pharmacokinetics , neuroprotection , pharmacology , spinal cord injury , amyotrophic lateral sclerosis , population , anesthesia , spinal cord , disease , environmental health , psychiatry
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.