Metabolites of bictegravir

Abstract

The present invention provides metabolites of the antiviral drug bictegravir, including compositions and salts thereof, which are useful in the prevention and/or treatment of HIV as well as analytical methods related to the administration of bictegravir.

1 . (canceled) 
     
     
         2 . A composition comprising a compound selected from M15, M20, and M23: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein the compound, or a pharmaceutically acceptable salt thereof, is present in the composition in an amount greater than about 25% by weight. 
       
     
     
         3 . The composition of  claim 2  wherein the compound, or a pharmaceutically acceptable salt thereof, is present in the composition in an amount greater than about 50% by weight. 
     
     
         4 . The composition of  claim 2  wherein the compound, or a pharmaceutically acceptable salt thereof, is present in the composition in an amount greater than about 75% by weight. 
     
     
         5 . (canceled) 
     
     
         6 . A pharmaceutical composition comprising a compound selected from M15, M20, and M23: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, and a least one pharmaceutically acceptable carrier. 
       
     
     
         7 . The pharmaceutical composition of  claim 6  further comprising one to three additional therapeutic agents. 
     
     
         8 . The pharmaceutical composition of  claim 7  wherein the one to three additional therapeutic agents is an anti-HIV agent. 
     
     
         9 . The pharmaceutical composition of  claim 8  wherein each of the one to three additional therapeutic agents is selected from the group consisting of HIV protease inhibitors, HIV non-nucleoside inhibitors of reverse transcriptase, HIV nucleoside inhibitors of reverse transcriptase, HIV nucleotide inhibitors of reverse transcriptase, and combinations thereof. 
     
     
         10 . A method of preventing or treating an HIV infection in a human comprising administering to the human a therapeutically effective amount of a compound selected from M15, M20, and M23: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         11 . The method of  claim 10  further comprising administering to the human a therapeutically effective amount of one to three additional therapeutic agents. 
     
     
         12 . The method of  claim 11  wherein the one to three additional therapeutic agents is an anti-HIV agent. 
     
     
         13 . The method of  claim 12  wherein the one to three additional therapeutic agents is selected from the group consisting of HIV protease inhibitors, HIV non-nucleoside inhibitors of reverse transcriptase, HIV nucleoside inhibitors of reverse transcriptase, HIV nucleotide inhibitors of reverse transcriptase, and other drugs for treating HIV, and combinations thereof. 
     
     
         14 . A method of detecting or confirming the administration of bictegravir to a patient comprising identifying a compound selected from M15, M20, and M23: 
       
         
           
           
               
               
           
         
         or a salt thereof, in a biological sample obtained from the patient. 
       
     
     
         15 . The method of  claim 14  wherein the biological sample is derived from plasma, urine, or feces. 
     
     
         16 . A method of measuring the rate of metabolism of bictegravir in a patient comprising measuring the amount of a compound selected from M15, M20, and M23: 
       
         
           
           
               
               
           
         
         or a salt thereof, in the patient at one or more time points after administration of bictegravir. 
       
     
     
         17 . The method of  claim 16  wherein the amount of compound is measured from a blood sample. 
     
     
         18 . The method of  claim 16  wherein the amount of compound is measured from plasma. 
     
     
         19 . The method of  claim 16  wherein the amount of compound is measured from a urine sample. 
     
     
         20 . The method of  claim 16  wherein the amount of compound is measured from a feces sample. 
     
     
         21 . A method of determining the prophylactic or therapeutic response of a patient to bictegravir in the treatment of HIV infection comprising measuring the amount of a compound selected from M15, M20, and M23: 
       
         
           
           
               
               
           
         
         or a salt thereof, in the patient at one or more time points after administration of bictegravir. 
       
     
     
         22 . A method of optimizing the dose of bictegravir for a patient in need of treatment with bictegravir comprising measuring the amount of a compound selected from M15, M20, and M23: 
       
         
           
           
               
               
           
         
         or a salt thereof, in the patient at one or more time points after administration of bictegravir.