Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent

Ashley Nguyen; Diana S.L. Chow; Lei Wu; Yang Teng; Mahua Sarkar; Elizabeth G. Toups; James S. Harrop; Karl M. Schmitt; Michele M. Johnson; James D. Guest; Bizhan Aarabi; Christopher I. Shaffrey; Maxwell Boakye; Ralph F. Frankowski; Michael G. Fehlings; Robert G. Grossman

doi:10.1002/jcph.1876

Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent

Ashley Nguyen, Diana S.L. Chow, Lei Wu, Yang Teng, Mahua Sarkar, Elizabeth G. Toups, James S. Harrop, Karl M. Schmitt, Michele M. Johnson, James D. Guest, Bizhan Aarabi, Christopher I. Shaffrey, Maxwell Boakye, Ralph F. Frankowski, Michael G. Fehlings, Robert G. Grossman

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1232-1242
Number of pages	11
Journal	Journal of Clinical Pharmacology
Volume	61
Issue number	9
DOIs	https://doi.org/10.1002/jcph.1876
State	Published - Sep 2021

Keywords

pharmacokinetics
population modeling
riluzole
spinal cord injury

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

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10.1002/jcph.1876

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Nguyen, A., Chow, D. S. L., Wu, L., Teng, Y., 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

Nguyen, A, Chow, DSL, Wu, L, Teng, Y, Sarkar, M, Toups, EG, Harrop, JS, Schmitt, KM, Johnson, MM, Guest, JD, Aarabi, B, Shaffrey, CI, Boakye, M, Frankowski, RF, Fehlings, MG & Grossman, RG 2021, 'Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent', Journal of Clinical Pharmacology, vol. 61, no. 9, pp. 1232-1242. https://doi.org/10.1002/jcph.1876

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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.}",

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AU - Guest, James D.

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AU - Shaffrey, Christopher I.

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Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent

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