Treatment of portal hypertension and cirrhosis
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Publication Number
US-11883400-B2
Publication Date
2024-01-30
Expiration Date
Abstract
Methods and formulations are provided for the treatment and prevention of portal hypertension.
Core Innovation
The invention relates to a method for treating a subject suffering from portal hypertension by administering ambrisentan. The method includes administering ambrisentan to a treated subject in an effective amount while maintaining plasma levels of ambrisentan below 10 ng/ml.
For portal hypertension associated with cirrhosis, the invention provides a related method in which ambrisentan is administered in an effective amount with plasma ambrisentan levels maintained below 10 ng/ml. The disclosure contrasts selective ETA antagonism with the potential effects of ETB antagonism, in which blocking ETB is described as removing vasodilation and risking a loss of portal-pressure reduction while potentially increasing renal fluid retention.
The disclosure states that maintaining ambrisentan below 10 ng/ml is intended to avoid significant ETB antagonism and to support portal pressure reduction and related clinical outcomes in portal hypertension and cirrhosis complications. The document further describes target outcomes using HVPG reduction thresholds and includes a clinical Example 10 in which low-concentration ambrisentan reduced HVPG while higher concentrations increased HVPG in cirrhosis/portal hypertension subjects.
Claims Coverage
The partial content provides two independent claims covering ambrisentan-based treatment of portal hypertension, with a shared pharmacokinetic limitation that plasma levels of ambrisentan are maintained below 10 ng/ml. Both independent claims specify treatment of portal hypertension, one generally and one explicitly in portal hypertension associated with cirrhosis.
Low plasma ambrisentan for portal hypertension
Administering an effective amount of ambrisentan to a subject suffering from portal hypertension, maintaining plasma levels of ambrisentan below 10 ng/ml.
Low plasma ambrisentan for portal hypertension associated with cirrhosis
Administering an effective amount of ambrisentan to a subject suffering from portal hypertension associated with cirrhosis, maintaining plasma levels of ambrisentan below 10 ng/ml.
Across both independent claims, the inventive coverage centers on administering ambrisentan at an effective amount while maintaining plasma levels below 10 ng/ml, with one claim directed to portal hypertension generally and the other to portal hypertension associated with cirrhosis.
Stated Advantages
Reduces HVPG when ambrisentan is administered at low concentrations.
Avoids significant ETB antagonism by maintaining plasma levels of ambrisentan below 10 ng/ml.
Higher concentrations of ambrisentan are described as increasing HVPG in cirrhosis/portal hypertension subjects.
Documented Applications
Treatment of portal hypertension.
Treatment of portal hypertension associated with cirrhosis.
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