High-Dose Macitentan for Pulmonary Arterial Hypertension
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for pulmonary arterial hypertension (PAH) often result in clinically relevant hemoglobin decreases, blood pressure changes, and edema, limiting their effectiveness and safety for improving disease status and long-term survival.
Innovation Solution
Administering high doses of macitentan, an endothelin receptor antagonist, ranging from 60 to 90 mg per day, to treat mild or moderate PAH, combined with other medications like PDE5 inhibitors, prostacyclin analogues, or soluble guanylate cyclase stimulators, to improve functional capacity and reduce morbidity and mortality risk.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for PAH are administered, then disease status and survival are improved, but hemoglobin decreases, blood pressure changes, and edema occur
Solution Approach 1:
The patent applies parameter changes by modifying the dosage of macitentan from conventional doses (10 mg/day) to high doses (60-90 mg/day). This parameter change resolves the technical contradiction by achieving superior disease status improvement and survival benefits while the patent demonstrates that high-dose macitentan maintains safety profiles without significant hemoglobin decreases, blood pressure changes, or edema, thus overcoming the harmful side effects associated with current treatments
2Productivity
If high-dose macitentan is administered, then functional capacity is enhanced and hospitalization rates decrease, but side effects such as hemoglobin decreases and edema may occur
Solution Approach 1:
The patent applies parameter changes by administering macitentan at high doses of 60-90 mg/day, which resolves the technical contradiction by significantly enhancing functional capacity and decreasing hospitalization rates. The patent data demonstrates that this high-dose regimen achieves superior clinical outcomes while maintaining an acceptable safety profile without significant hemoglobin decreases or edema, thus overcoming the side effects that would normally limit treatment effectiveness
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
High-dose macitentan treatment stabilizes or improves PAH status, enhances functional class, and decreases hospitalization rates without significant side effects such as hemoglobin decreases or edema, thereby improving long-term survival and reducing morbidity and mortality risk.
Implementation Method 1
macitentan, an endothelin receptor antagonist
Data Source
Figure 1
AI summary
The present invention relates to high doses of macitentan, i.e. propylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl]-amide or pharmaceutically acceptable salts, solvates, hydrates or morphological forms thereof, or of aprocitentan, for use in the treatment and/or prevention of pulmonary arterial hypertension (PAH). Moreover, the present invention relates to the use of high doses of macitentan, or of aprocitentan, for the manufacture of a medicament for the treatment and/or prevention of PAH, as well as to a method for the treatment and/or prevention of PAH comprising high doses of macitentan or of aprocitentan. Further, the present invention relates to a dosage regimen for the treatment and/or prevention of PAH as well as to a combination of macitentan, or of aprocitentan, with one or more phosphodiesterase type 5 (PDE5) inhibitors, prostacyclin analogues, prostacyclin receptor agonists or soluble guanylate cyclase stimulators. Therein, PAH is preferably mild or moderate PAH. Moreover, the present invention relates to a pharmaceutical composition for the treatment of PAH comprising a high dose of macitentan or of aprocitentan.