Use of avermectin derivative for increasing bioavailability and efficacy of macrocylic lactones

Abstract

The present invention relates to the use of avermectin derivative as a drug for the treatment of parasitic infections. The avermectin derivative is represented by the formula (I) where: (i) R1 is chosen from the group constituted of —CH(CH3)2, —CH(CH3)CH2CH3, or cyclohexyl, (ii) X represents —CH2—CH2—, or —CH═CH—, (iii) R2 is chosen fromor an OH group, (iv) R3 is OH or NOH, (v) represents a single bond when R3 is OH, or a double bond when R3 is NOH, as an inhibitor of a membrane-bound protein which transports exogenous compounds out of target cells.

1 . A pharmaceutical composition comprising a compound of formula I 
       
         
           
           
               
               
           
         
       
       wherein
 (i) R 1  is selected from the group consisting of —CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , or cyclohexyl 
 (ii) X represents —CH═CH— or —CH 2 —CH 2 —, wherein X is —CH 2 —CH 2 — only when R 1  is cyclohexyl; 
 (iii) R 2  is —OH, and 
 (iv)  R 3  is OH or NOH; 
 a second active ingredient selected from the group consisting of a macrocyclic lactone antiparasitic agent, an antitumoral agent, an antiviral agent, an anti-epileptic agent, an antibacterial agent, and an antifungal agent, wherein the second active ingredient is a compound other than a compound of formula I; 
 and, 
 a pharmaceutically acceptable carrier, 
 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein
 (i) R 1  is selected from the group consisting of —CH(CH 3 ) 2 , and —CH(CH 3 )CH 2 CH 3 ,   (ii) X represents —CH═CH—,   (iii) R 2  is —OH, and   (iv)  R 3  is OH,   said compound corresponding to the compound of formula I(c):   
       
         
           
           
               
               
           
         
       
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein
 (i) R 1  is cyclohexyl,   (ii) X represents —CH═CH—,   (iii) R 2  is —OH, and   (iv)  R 3  is OH,   said compound corresponding to a compound of formula I(d):   
       
         
           
           
               
               
           
         
       
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein
 (i) R 1  is cyclohexyl,   (ii) X represents —CH 2 —CH 2 —,   (iii) R 2  is —OH, and   (iv)  R 3  is ═NOH,   said compound corresponding a compound of formula I(e):   
       
         
           
           
               
               
           
         
       
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the second active ingredient is chosen from an antiplasmodium, or an antileshmania agent. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the second active ingredient is an antiviral agent. 
     
     
         7 . A method of treatment of infections comprising administering to a subject in need thereof a pharmaceutical composition of  claim 1 . 
     
     
         8 . The method of  claim 7 , wherein the infection is a viral infection, a bacterial infection or a fungal infection wherein the second active ingredient is an antiviral agent, antibacterial agent or an antifungal agent, respectively.