Method for improving pharmacokinetics

Abstract

The object of the present invention is to inhibit oxidative metabolism of a compound of formula I by co-administration with ritonavir, a cytochrome P450 inhibitor.

We claim: 
     
         1 . A method of inhibiting in vivo oxidative metabolism of a Hepatitis C virus NS3/4A protease inhibitor according to formula I in a patient comprising co-administering 
       
         
           
           
               
               
           
         
       
       a compound of formula I and a cytochrome P450 monooxygenase wherein the cytochrome P450 monooxygenase inhibitor is ritonavir. 
     
     
         2 . The method according to  claim 1  wherein the compound of formula I and ritonavir are in separate dosage forms. 
     
     
         3 . The method according to  claim 2  wherein the separate dosage forms are administered about simultaneously. 
     
     
         4 . The method according to  claim 1  wherein the compound of formula I and ritonavir are administered in a single dosage form. 
     
     
         5 . The method according to  claim 2  wherein the dose of ritonavir is 50 to 400 mg/day and the dose of compound I was 25 to 600 mg/day. 
     
     
         6 . A method according to  claim 6  wherein the dose of ritonavir is 100 to 200 mg/day and the dose of compound I was 50 to 300 mg/day. 
     
     
         7 . A method for treating a Hepatitis C virus infection in a patient in need thereof comprising administering to the patient in need thereof a therapeutically effective amount of a Hepatitis C virus NS3/4A protease inhibitor of formula I, or free base or other pharmaceutically acceptable salt thereof, and a cytochrome P450 monooxygenase inhibitor wherein the cytochrome P450 monooxygenase inhibitor is ritonavir. 
     
     
         8 . The method according to  claim 7  which method comprises co-administering the compound of formula I and ritonavir and at least one additional agent selected from an immunomodulatory agent and/or an antiviral agent and/or another inhibitor of HCV NS3/4A protease and/or an inhibitor of NS5B polymerase and/or a broad-spectrum viral inhibitor and/or another cytochrome P-450 inhibitor. 
     
     
         9 . The method according to  claim 8 , wherein said immunomodulatory agent is α-, β- or γ-interferon or thymosin, said antiviral agent is ribavirin or said polymerase inhibitor is R7128. 
     
     
         10 . A pharmaceutical composition according to  claim 1 , and at least one pharmaceutically acceptable excipient, diluent or carrier. 
     
     
         11 . A kit comprising a Hepatitis C virus NS3 protease inhibitor according to formula I and ritonavir. 
     
     
         12 . A pharmaceutical pack containing comprising a compound according to formula I and ritonavir together with an information insert containing directions for the use of the inhibitors.