Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent.
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2021-09
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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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Nguyen, Ashley, Diana S-L Chow, Lei Wu, Yang Angela Teng, Mahua Sarkar, Elizabeth G Toups, James S Harrop, Karl M Schmitt, et al. (2021). Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent. Journal of clinical pharmacology, 61(9). pp. 1232–1242. 10.1002/jcph.1876 Retrieved from https://hdl.handle.net/10161/28074.
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Christopher Ignatius Shaffrey
I have more than 25 years of experience treating patients of all ages with spinal disorders. I have had an interest in the management of spinal disorders since starting my medical education. I performed residencies in both orthopaedic surgery and neurosurgery to gain a comprehensive understanding of the entire range of spinal disorders. My goal has been to find innovative ways to manage the range of spinal conditions, straightforward to complex. I have a focus on managing patients with complex spinal disorders. My patient evaluation and management philosophy is to provide engaged, compassionate care that focuses on providing the simplest and least aggressive treatment option for a particular condition. In many cases, non-operative treatment options exist to improve a patient’s symptoms. I have been actively engaged in clinical research to find the best ways to manage spinal disorders in order to achieve better results with fewer complications.
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