Method for improving pharmacokinetics

Abstract

The object of the present invention is to elevate the blood levels of a compound of formula I by co-administration with a cytochrome P450 inhibitor.

1 . A method for increasing the bioavailability of a Hepatitis C virus NS3/4A protease inhibitor according to formula I in a patient comprising co-administering to the patient a 
       
         
           
           
               
               
           
         
       
       compound of formula I and a cytochrome P450 monooxygenase inhibitor wherein the monooxygenase inhibitor is present sufficient amount to elevate the blood levels of I. 
     
     
         2 . A method according to  claim 1  wherein the cytochrome P450 monooxygenase inhibitor is ritonavir. 
     
     
         3 . The method according to  claim 2  wherein the compound of formula I and ritonavir are in separate dosage forms. 
     
     
         4 . The method according to  claim 3  wherein the separate dosage forms are administered about simultaneously. 
     
     
         5 . The method according to  claim 2  wherein the compound of formula I and ritonavir are administered in a single dosage form. 
     
     
         6 . 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. 
     
     
         7 . 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. 
     
     
         8 . A method for treating a Hepatitis C virus infection in a patient in need thereof comprising administering to the patient in need thereof the compound of formula I, or free base or other pharmaceutically acceptable salt thereof, and a cytochrome P450 monooxygenase inhibitor, or a pharmaceutically acceptable salt thereof. 
     
     
         9 . A method according to  claim 11  wherein the cytochrome P450 monooxygenase inhibitor is ritonavir, or a pharmaceutically acceptable salt thereof. 
     
     
         10 . The method according to  claim 9  which method comprises co-administering along with a compound of formula I and ritonavir, 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. 
     
     
         11 . The method according to  claim 10 , wherein said immunomodulatory agent is α-, β- or γ-interferon or thymosin, said antiviral agent is ribavirin or said polymerase inhibitor is R7128. 
     
     
         12 . The method of  claim 10  wherein the inhibitor of NS5B polymerase is R7128. 
     
     
         13 . A pharmaceutical composition comprising a compound of formula I, or free base or other pharmaceutically acceptable salt thereof, and a cytochrome P450 monooxygenase inhibitor or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, diluent or carrier. 
     
     
         14 . A pharmaceutical composition according to  claim 13  wherein the cytochrome P450 monooxygenase inhibitor is ritonavir, or a pharmaceutically acceptable salt thereof. 
     
     
         15 . A kit comprising a Hepatitis C virus NS3 protease inhibitor according to formula I and ritonavir. 
     
     
         16 . A pharmaceutical pack containing comprising a compound according to formula I, ritonavir, and an information insert containing directions for the use of the inhibitors.