Riluzole Exposure Variability Reduction via CK-2017357
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for ALS, particularly riluzole, face challenges due to variability in serum and plasma concentrations, leading to difficulties in determining effective doses and increasing the incidence and severity of adverse events.
Innovation Solution
The use of CK-2017357 in combination with riluzole, which acts as a selective activator of the fast skeletal muscle troponin complex, reduces variability in riluzole exposure and allows for lower doses of riluzole, potentially improving patient outcomes and reducing adverse events.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If riluzole is administered to treat ALS, then therapeutic effect is achieved, but variability in serum and plasma concentrations leads to difficulties in determining effective doses and increases incidence and severity of adverse events
Solution Approach 1:
The patent applies parameter changes by modifying the pharmacokinetic parameters of riluzole through combination therapy with CK-2017357. Specifically, CK-2017357 increases the half-life and exposure of riluzole, transforming the concentration-time profile to achieve more consistent therapeutic levels while reducing peak-related adverse events.
2Reliability
If riluzole is administered to treat ALS, then therapeutic effect is achieved, but variability in serum and plasma concentrations makes it difficult to determine effective doses
Solution Approach 1:
The patent employs feedback mechanisms through pharmacokinetic monitoring and dose adjustment based on individual patient responses. By measuring serum and plasma concentrations and using this information to guide dosing decisions, the therapy achieves more precise dosage determination while maintaining therapeutic effectiveness.
3Reliability
If CK-2017357 is administered in combination with riluzole, then variability in riluzole exposure is reduced and lower doses are achieved, but drug interaction mechanisms must be managed
Solution Approach 1:
The patent uses CK-2017357 as an intermediary agent that modulates the pharmacokinetics of riluzole. This mediator increases riluzole exposure and reduces variability through its effect on metabolism and clearance, allowing for more consistent therapeutic levels while enabling lower riluzole doses.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
CK-2017357 increases the exposure and half-life of riluzole, reduces variability in plasma concentrations, and allows for a decrease in the total daily dose of riluzole, thereby improving activities of daily living and potentially prolonging survival in ALS patients while minimizing adverse events.
Implementation Method 1
CK-2017357 is a selective activator of the fast skeletal muscle troponin complex, which sensitizes fast skeletal muscle to calcium and results in an amplification of the response to neuromuscular input
Implementation Method 2
CK-2017357 increases the exposure and half-life of riluzole, reduces variability in plasma concentrations
Data Source
Figure 1
Figure 2
Figure 3
AI summary
Provided is a method for treating ALS in a subject, comprising administering to the subject a therapeutically effective amount of riluzole and a therapeutically effective amount of CK-2017357. Also provided are methods of reducing the variability of riluzole exposure (e.g., Cmax and/or AUC24h) in a subject, methods of reducing the variability of riluzole exposure (e.g., Cmax and/or AUC24h) between two or more subjects, methods of decreasing the total daily dose of riluzole in a subject, methods of increasing the half-life of riluzole in a subject, methods for decreasing the frequency of riluzole dosing in the subject, and methods for reducing the incidence and/or severity of adverse events in a subject treated with riluzole.