Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent
| Autor: | Diana S.-L. Chow, James D. Guest, Michele M. Johnson, Robert G. Grossman, Karl M. Schmitt, Christopher I. Shaffrey, Mahua Sarkar, Yang Angela Teng, James S. Harrop, Elizabeth G. Toups, Maxwell Boakye, Michael G. Fehlings, Ralph F. Frankowski, Ashley Nguyen, Lei Wu, Bizhan Aarabi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Time Factors
Metabolic Clearance Rate Population Pharmacology 030226 pharmacology & pharmacy Neuroprotection Models Biological 03 medical and health sciences 0302 clinical medicine Sodium channel blocker Pharmacokinetics Double-Blind Method medicine Humans Pharmacology (medical) Amyotrophic lateral sclerosis education Spinal cord injury Spinal Cord Injuries education.field_of_study Riluzole Clinical Trials Phase I as Topic Dose-Response Relationship Drug business.industry Therapeutic effect medicine.disease spinal cord injury Neuroprotective Agents 030220 oncology & carcinogenesis business population modeling medicine.drug Half-Life |
| Zdroj: | Journal of Clinical Pharmacology |
| ISSN: | 1552-4604 |
| Popis: | Riluzole, a benzothiazole sodium channel blocker that received FDA approval to attenuate neurodegeneration in amyotrophic lateral sclerosis (ALS) 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 one-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 I and the ongoing Phase II/III 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. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text