Methods of reducing small, dense ldl particles

Abstract

The present invention provides methods for increasing LDL particle size.

1 . A method of decreasing the amount of small, dense LDL particles in a human having LDL particle size pattern I or B, the method comprising,
 administering a therapeutically-effective amount of a compound of Formula I or a salt, prodrug or isomer thereof to the human wherein the LDL particle size pattern is changed after administration:   from pattern Ito pattern A; or   from pattern B to pattern I or A.   
   
   
       2 . The method of  claim 1 , wherein the human has a lower level of LDL-III particles after the administrating step compared to prior to the administering step. 
   
   
       3 . The method of  claim 1 , wherein the human has a lower level of LDL-IV particles after the administrating step compared to prior to the administering step. 
   
   
       4 . The method of  claim 1 , wherein the compound is 
     
       
         
         
             
             
         
       
     
     or a salt, prodrug or isomer thereof. 
   
   
       5 . The method of  claim 1 , wherein said compound is 
     
       
         
         
             
             
         
       
     
     or a salt or prodrug thereof. 
   
   
       6 . The method of  claim 1 , wherein the human has an LDL particle size pattern A after 10 days after the administering step. 
   
   
       7 . The method of  claim 1 , further comprising measuring the LDL particle diameter of the human prior to the administering step. 
   
   
       8 . The method of  claim 1 , further comprising measuring the LDL particle diameter of the human after the administering step. 
   
   
       9 . The method of  claim 1 , wherein the human has an LDL particle size pattern B prior to the administering step. 
   
   
       10 . The method of  claim 1 , wherein Apolipoprotein B-100 blood levels are reduced at least 10% after 10 days of the administering step. 
   
   
       11 . The method of  claim 1 , wherein absorption of cholesterol is reduced by least 5% after 10 days of the administering step. 
   
   
       12 . The method of  claim 1 , wherein cholesterol synthesis is reduced at least 5% after 10 days of the administering step. 
   
   
       13 . A method of reducing triglycerides and LDL blood levels in a human having LDL particle size pattern I or B, the method comprising
 administering a therapeutically-effective amount of a compound of Formula I or a salt, prodrug or isomer thereof to the human wherein the LDL particle size pattern is changed after administration:   from pattern Ito pattern A; or   from pattern B to pattern I or A.   
   
   
       14 . The method of  claim 13 , wherein the compound is 
     
       
         
         
             
             
         
       
     
     or a salt, prodrug or isomer thereof. 
   
   
       15 . The method of  claim 13 , wherein said compound is 
     
       
         
         
             
             
         
       
     
     or a salt or prodrug thereof. 
   
   
       16 . The method of  claims 13 , further comprising administrating a statin to the human. 
   
   
       17 . The method of  claim 16 , wherein the statin is Atorvastatin. 
   
   
       18 . A method of identifying a candidate individual for treatment with a compound of Formula I or a salt, prodrug or isomer thereof, the method comprising,
 measuring the LDL peak particle diameter of an individual; and   administering the compound to the individual if the individual had a pattern I or B LDL particle size pattern.   
   
   
       19 . The method of  claim 18 , wherein the individual has a pattern I LDL particle size pattern and the compound is administered to the individual after the measuring step. 
   
   
       20 . The method of  claim 18 , wherein the individual has a pattern B LDL particle size pattern and the compound is administered to the individual after the measuring step.