Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent
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...
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Published in | Journal of clinical pharmacology Vol. 61; no. 9; pp. 1232 - 1242 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
01.09.2021
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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ISSN: | 0091-2700 1552-4604 |
DOI: | 10.1002/jcph.1876 |