Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent.
Publication/Presentation Date
9-1-2021
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.
Volume
61
Issue
9
First Page
1232
Last Page
1242
ISSN
1552-4604
Published In/Presented At
Nguyen, A., Chow, D. S., Wu, L., Teng, Y. A., Sarkar, M., Toups, E. G., Harrop, J. S., Schmitt, K. M., Johnson, M. M., Guest, J. D., Aarabi, B., Shaffrey, C. I., Boakye, M., Frankowski, R. F., Fehlings, M. G., & Grossman, R. G. (2021). Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent. Journal of clinical pharmacology, 61(9), 1232–1242. https://doi.org/10.1002/jcph.1876
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
33908635
Department(s)
Administration and Leadership
Document Type
Article