Bupropion Co-Administration to Sustain Dextromethorphan Plasma Levels
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for a treatment to increase plasma levels of dextromethorphan in human beings who are extensive metabolizers, as they rapidly metabolize the drug, limiting its clinical utility.
Innovation Solution
Co-administering bupropion or its derivatives, such as erythrohydroxybupropion or threohydroxybupropion, with dextromethorphan to inhibit its metabolism, thereby increasing and sustaining plasma levels of dextromethorphan.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dextromethorphan is administered to extensive metabolizers, then the drug is rapidly metabolized and eliminated, but plasma levels are insufficient for therapeutic efficacy
Solution Approach 1:
The patent introduces bupropion and its metabolites as intermediary substances that mediate between dextromethorphan administration and its metabolic breakdown. These intermediaries inhibit CYP2D6 enzyme activity, thereby protecting dextromethorphan from rapid metabolism and maintaining therapeutic plasma levels in extensive metabolizers
Solution Approach 2:
The patent changes the pharmacokinetic parameters of dextromethorphan by co-administering bupropion, which alters the metabolic rate and plasma concentration-time profile. This parameter change transforms dextromethorphan from a rapidly eliminated drug into one with sustained therapeutic levels
2Reliability
If dextromethorphan is administered frequently to maintain plasma levels, then therapeutic coverage is improved, but treatment complexity and patient compliance worsen
Solution Approach 1:
The patent achieves continuous therapeutic action through a single daily dose of dextromethorphan combined with bupropion, eliminating the need for multiple daily administrations. The bupropion provides sustained CYP2D6 inhibition, maintaining continuous plasma level enhancement throughout the dosing interval
3Reliability
If dextromethorphan plasma levels are increased in extensive metabolizers, then therapeutic efficacy is improved, but adverse events may increase
Solution Approach 1:
The patent applies partial inhibition of CYP2D6 enzyme activity rather than complete inhibition, achieving sufficient plasma level enhancement for therapeutic efficacy while avoiding excessive accumulation that would lead to adverse events. The bupropion metabolites provide moderate, controlled inhibition
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
The co-administration of bupropion derivatives with dextromethorphan results in higher and more sustained plasma levels, reducing the frequency of doses required while minimizing adverse events and enhancing therapeutic efficacy.
Implementation Method 1
bupropion for use in a method of increasing dextromethorphan plasma levels... co-administering bupropion with dextromethorphan... to inhibit its metabolism
Data Source
Figure 1
Figure 2
Figure 3
AI summary
This disclosure relates to methods administering erythrohydroxybupropion or a prodrug thereof in conjunction with dextromethorphan to a human being. Dosage forms, drug delivery systems, and methods related to dextromethorphan or dextrorphan and erythrohydroxybupropion or a prodrug of erythrohydroxybupropion are also disclosed.