Dextromethorphan Metabolism Inhibition via Bupropion Co-Administration

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Dextromethorphan has limited systemic drug exposure due to rapid hepatic metabolism in extensive metabolizers, limiting its clinical utility as a single agent for treating neurological disorders.

Innovation Solution

Co-administration of bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion with dextromethorphan to inhibit its metabolism, thereby increasing plasma levels and extending its metabolic lifetime, which can be administered less frequently without loss of efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If dextromethorphan is administered alone, then it provides antitussive and neurological effects, but rapid hepatic metabolism limits systemic drug exposure and therapeutic efficacy

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidmetabolic lifetime

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent introduces bupropion and its metabolites (hydroxybupropion, erythrohydroxybupropion, threohydroxybupropion) as intermediary substances that inhibit CYP2D6 enzyme activity. These intermediaries block the metabolic pathway of dextromethorphan, preventing its rapid conversion to dextrorphan and other metabolites, thereby extending dextromethorphan's metabolic lifetime and enhancing its therapeutic efficacy in extensive metabolizers

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If dextromethorphan is administered frequently to maintain plasma levels, then therapeutic efficacy is improved, but dosing frequency increases and convenience decreases

Engineering Contradiction:

Improveplasma concentration maintenanceVSAvoiddosing frequency

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

Bupropion and its metabolites serve as intermediary agents that significantly extend the half-life of dextromethorphan by inhibiting its metabolism. This extension allows for less frequent dosing (e.g., once or twice daily instead of multiple times daily) while maintaining effective plasma concentrations, thereby improving ease of operation without compromising therapeutic reliability

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a dynamic system where bupropion metabolites continuously inhibit CYP2D6 enzyme activity throughout the dosing interval. This dynamic inhibition adapts to the dosing regimen, allowing flexible dosing frequencies while maintaining stable dextromethorphan plasma levels, thus resolving the contradiction between plasma concentration maintenance and dosing convenience

Inventive Principle:

Principle #15Dynamics

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

This approach enhances the therapeutic efficacy of dextromethorphan by maintaining effective plasma concentrations and reducing the frequency of dosing, improving antitussive and neurological disorder treatment outcomes.

Implementation Method 1

Co-administration of bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion with dextromethorphan to inhibit its metabolism

Methodology Applied

Scientific EffectEnzyme inhibition: Enzyme

Data Source

PatentUS11147808B2Method of decreasing the fluctuation index of dextromethorphan

Publication Date: 2021.10.19 ANTECIP BIOVENTURES II LLC

AI summary

Dosage forms, drug delivery systems, and methods related to sustained release of dextromethorphan or improved therapeutic effects are disclosed. Typically, bupropion or a related compound is orally administered to a human being to be treated with, or being treated with, dextromethorphan.