Compositons and methods of use of ritonavir for treating hcv

Abstract

The present invention discloses compositions and a method of improving the pharmacokinetics of pharmaceutical agents (or pharmaceutically acceptable salts, esters, and prodrugs thereof) which are metaboilized by cytochrome P450 monoxygenase comprising coadministering ritonavir or a pharmaceutically acceptable salt, ester, and prodrug thereof.

1 . A pharmaceutical coadministered composition comprising 2-(2-{2-cyclohexyl-2[(pyrazine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid(1-cyclopropylaminooxalyl-butyl)-amide (VX-950) or a salt, ester, or prodrug thereof and ritonavir or a salt, ester, or prodrug thereof.  
   
   
       2 . A method for improving the pharmacokinetics of 2-(2-{2-cyclohexyl-2[(pyrazine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid(1-cyclopropylaminooxalyl-butyl)-amide (VX-950), or a salt, ester, or prodrug thereof comprising coadministering 2-(2-{2-cyclohexyl-2[(pyrazine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid(1-cyclopropylaminooxalyl-butyl)-amide (VX-950) or a salt, ester, or prodrug thereof with ritonavir or a salt, ester, or prodrug thereof.  
   
   
       3 . A pharmaceutical coadministered composition comprising 3-[2-(3-tert-butyl-ureido)-3,3-diemthyl-butyryl]-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid (2-carbamoyl-1-cyclobutylmethyl-2-oxo-ethyl)-amide (SCH 503034) or a salt, ester, or prodrug thereof and ritonavir or a salt, ester, or prodrug thereof.  
   
   
       4 . A method for improving the pharmacokinetics of 3-[2-(3-tert-butyl-ureido)-3,3-diemthyl-butyryl]-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid (2-carbamoyl-1-cyclobutylmethyl-2-oxo-ethyl)-amide (SCH 503034) or a salt, ester, or prodrug thereof comprising coadministering 3-[2-(3-tert-butyl-ureido)-3,3-diemthyl-butyryl]-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid (2-carbamoyl-1-cyclobutylmethyl-2-oxo-ethyl)-amide (SCH 503034) or a salt, ester, or prodrug thereof with ritonavir or a salt, ester, or prodrug thereof.  
   
   
       5 . A composition of  claim 1  coadministered with one or more pharmaceutical agents selected from the group consisting of interferon alpha-2a, interferon alpha-2b, pegylated interferon, pegylated interferon alpha-2a, pegylated interferon alpha-2b, concensus interferon alpha, pegylated concensus-inteferon alpha, interferon fused to a protein, ribavirin, and viramidine.  
   
   
       6 . A composition of  claim 3  coadministered with one or more pharmaceutical agents selected from the group consisting of interferon alpha-2a, interferon alpha-2b, pegylated interferon, pegylated interferon alpha-2a, pegylated interferon alpha-2b, concensus interferon alpha, pegylated concensus-inteferon alpha, interferon fused to a protein, ribavirin, and viramidine.  
   
   
       7 . A method for treating HCV in a mammal comprising coadministering 2-(2-{2-cyclohexyl-2[(pyrazine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid( 1-cyclopropylaminooxalyl-butyl)-amide (VX-950), or a salt, ester, or prodrug thereof and ritonavir or a salt, ester, or prodrug thereof.  
   
   
       8 . A method for treating HCV in a mammal comprising coadmistering 2-(2-{2-cyclohexyl-2[(pyrazine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid(1-cyclopropylaminooxalyl-butyl)-amide (VX-950), or a salt, ester, or prodrug thereof and ritonavir or a salt, ester, or prodrug thereof, and further coadmistering with one or more pharmaceutical agents selected from the group consisting of interferon alpha-2a, interferon alpha-2b, pegylated interferon, pegylated interferon alpha-2a, pegylated interferon alpha-2b, concensus interferon alpha, pegylated concensus-inteferon alpha, interferon fused to a protein, ribavirin, and viramidine.  
   
   
       9 . A method for treating HCV comprising coadminstering 3-[2-(3-tert-butyl-ureido)-3,3-diemthyl-butyryl]-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid (2-carbamoyl-1-cyclobutylmethyl-2-oxo-ethyl)-amide (SCH 503034) or a salt, ester, or prodrug thereof comprising and ritonavir or a salt, ester, or prodrug thereof.  
   
   
       10 . A method for treating HCV comprising coadminstering 3-[2-(3-tert-butyl-ureido)-3,3-diemthyl-butyryl]-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid (2-carbamoyl-1-cyclobutylmethyl-2-oxo-ethyl)-amide (SCH 503034) or a salt, ester, or prodrug thereof comprising and ritonavir or a salt, ester, or prodrug thereof, and further coadministering with one or more pharmaceutical agents selected from the group consisting of interferon alpha-2a, interferon alpha-2b, pegylated interferon, pegylated interferon alpha-2a, pegylated interferon alpha-2b, concensus interferon alpha, pegylated concensus-inteferon alpha, interferon fused to a protein, ribavirin, and viramidine.  
   
   
       11 . A method of inhibiting HCV in a mammal comprising coadministering 2-(2-{2-cyclohexyl-2[(pyrazine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid( 1-cyclopropylaminooxalyl-butyl)-amide (VX-950), or a salt, ester, or prodrug thereof and ritonavir or a salt, ester, or prodrug thereof.  
   
   
       12 . A method of inhibiting HCV comprising coadminstering 3-[2-(3-tert-butyl-ureido)-3,3-diemthyl-butyryl]-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid (2-carbamoyl-1-cyclobutylmethyl-2-oxo-ethyl)-amide (SCH 503034) or a salt, ester, or prodrug thereof and ritonavir or a salt, ester, or prodrug thereof.