Method for Increasing the Bioavailability of the Active Form of S-[2-([[1-(2-Ethylbutyl)Cyclohexyl]Carbonyl] Amino)Phenyl] 2-Methylpropanethioate

Abstract

The invention is directed to a method of increasing the bioavailability of the active form of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate by administration of a therapeutically effective amount of the drug with food. The invention also provides a kit comprising a pharmaceutical composition comprising a therapeutically effective amount of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate and a pharmaceutically acceptable carrier, prescribing information, and a container, wherein the prescribing information includes advice to a patient regarding administration of the drug with food to improve bioavailability.

1 . A method of increasing the bioavailability of the active form of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate to a patient receiving S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate therapy comprising orally administering to the patient a therapeutically effective amount of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate in a pharmaceutical composition with food.  
     
     
         2 . The method of  claim 1 , wherein the therapeutically effective amount is about 100 mg to about 1800 mg.  
     
     
         3 . The method of  claim 2 , wherein the therapeutically effective amount is about 300 mg to about 900 mg.  
     
     
         4 . The method of  claim 1 , wherein the administration to the patient occurs between about 1 hour prior to consuming food to about 2 hours after consuming food.  
     
     
         5 . The method of  claim 4 , wherein the administration to the patient is substantially at the same time as the consumption of the food.  
     
     
         6 . The method of  claim 4 , wherein the administration to the patient is immediately after the consumption of food to up to about 1 hour after the consumption of food.  
     
     
         7 . The method of  claim 1 , wherein the pharmaceutical composition is in a unit dosage form of a tablet.  
     
     
         8 . The method of  claim 7 , wherein the tablet comprises about 100 mg to about 1800 mg of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate.  
     
     
         9 . The method of  claim 8 , wherein the tablet comprises about 300 mg of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate, and the therapeutically effective amount is about 300 mg to about 900 mg.  
     
     
         10 . The method of  claim 1 , wherein the administration results in an increase in the maximum plasma concentration of the active form of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate as compared to the administration of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate without food.  
     
     
         11 . The method of  claim 1 , wherein the pharmaceutical composition is provided to a patient in a container associated with prescribing information that advises the patient that the pharmaceutical composition is to be administered with food.  
     
     
         12 . The method of  claim 11 , wherein prescribing information further advises the patient that the administration of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-metlhylpropanethioate in a pharmaceutical composition with food results in an increase of the maximum plasma concentration of the active form of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate as compared to the administration of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate under fasted conditions.  
     
     
         13 . The method of  claim 11 , wherein the prescribing information further advises the patient to administer the pharmaceutical composition between about 1 hour prior to consuming food to about 2 hours after consuming food.  
     
     
         14 . The method of  claim 13 , wherein the prescribing information further advises the patient to administer the pharmaceutical composition substantially at the same time as consuming food.  
     
     
         15 . The method of  claim 13 , wherein the prescribing information further advises the patient to administer the pharmaceutical composition immediately after consuming food to up to about 1 hour after consuming food.  
     
     
         16 . A method of increasing the extent of absorption of the active form of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate as measured by the active form concentration attained in the blood stream over time in a patient in need of a therapeutic effect thereof comprising orally administering to the patient a therapeutically effective amount of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate in a pharmaceutical composition with food.  
     
     
         17 . The method of  claim 16 , wherein the therapeutically effective amount is about 100 mg to about 1800 mg.  
     
     
         18 . The method of  claim 17 , wherein the therapeutically effective amount is about 300 mg to about 900 mg.  
     
     
         19 . The method of  claim 16 , wherein the administration to the patient occurs between about 1 hour prior to consuming food to about 2 hours after consuming food.  
     
     
         20 . The method of  claim 19 , wherein the administration to the patient is substantially at the same time as the consumption of the food.  
     
     
         21 . The method of  claim 19 , wherein the administration to the patient is immediately after the consumption of food to up to about 1 hour after the consumption of food.  
     
     
         22 . The method of  claim 16 , wherein the pharmaceutical composition is in a unit dosage form of a tablet.  
     
     
         23 . The method of  claim 22 , wherein the tablet comprises about 100 mg to about 1800 mg of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate.  
     
     
         24 . The method of  claim 23 , wherein the tablet comprises about 300 mg of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate, and the therapeutically effective amount is about 300 mg to about 900 mg.  
     
     
         25 . A method for decreasing the activity of cholesteryl ester transfer protein (CETP) in a patient, which comprises orally administering to the patient a therapeutically effective amount of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate in a pharmaceutical composition with food.  
     
     
         26 . The method of  claim 25 , wherein the therapeutically effective amount is about 100 mg to about 1800 mg.  
     
     
         27 . The method of  claim 26 , wherein the therapeutically effective amount is about 300 mg to about 900 mg.  
     
     
         28 . The method of  claim 25 , wherein the administration to the patient occurs between about 1 hour prior to consuming food to about 2 hours after consuming food.  
     
     
         29 . The method of  claim 28 , wherein the administration to the patient is substantially at the same time as the consumption of the food.  
     
     
         30 . The method of  claim 28 , wherein the administration to the patient is immediately after the consumption of food to up to about 1 hour after the consumption of food.  
     
     
         31 . The method of  claim 25 , wherein the pharmaceutical composition is in a unit dosage form of a tablet.  
     
     
         32 . The method of  claim 31 , wherein the tablet comprises about 100 mg to about 1800 mg of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate.  
     
     
         33 . The method of  claim 32 , wherein the tablet comprises about 300 mg of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate, and the therapeutically effective amount is about 300 mg to about 900 mg.  
     
     
         34 . A method for the treatment or prophylaxis of a cardiovascular disorder in a patient comprising administering S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate to a patient, which comprises orally administering to the patient a therapeutically effective amount of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate in a pharmaceutical composition with food.  
     
     
         35 . The method of  claim 34 , wherein the cardiovascular disorder is selected from the group consisting of cardiovascular disease, coronary heart disease, coronary artery disease, hypoalphalipoproteinemia, hypercholesterolemia, and atherosclerosis.  
     
     
         36 . The method of  claim 34 , wherein the therapeutically effective amount is about 100 mg to about 1800 mg.  
     
     
         37 . The method of  claim 36 , wherein the therapeutically effective amount is about 300 mg to about 900 mg.  
     
     
         38 . The method of  claim 34 , wherein the administration to the patient occurs between about 1 hour prior to consuming food to about 2 hours after consuming food.  
     
     
         39 . The method of  claim 38 , wherein the administration to the patient is substantially at the same time as the consumption of the food.  
     
     
         40 . The method of  claim 38 , wherein the administration to the patient is immediately after the consumption of food to up to about 1 hour after the consumption of food.  
     
     
         41 . The method of  claim 34 , wherein the pharmaceutical composition is in a unit dosage form of a tablet.  
     
     
         42 . The method of  claim 41 , wherein the tablet comprises about 100 mg to about 1800 mg of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate.  
     
     
         43 . The method of  claim 42 , wherein the tablet comprises about 300 mg of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate, and the therapeutically effective amount is about 300 mg to about 900 mg.  
     
     
         44 . A lit comprising a pharmaceutical composition comprising a therapeutically effective amount of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate and a pharmaceutically acceptable carrier, prescribing information, and a container, wherein the prescribing information includes advice to a patient regarding administration of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate in a pharmaceutical composition with food.  
     
     
         45 . The kit of  claim 44 , wherein the prescribing information states that the administration of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate with food improves bioavailability.  
     
     
         46 . The kit of  claim 44 , wherein the therapeutically effective amount is about 100 mg to about 1800 mg.  
     
     
         47 . The kit of  claim 46 , wherein the therapeutically effective amount is about 300 mg to about 900 mg.  
     
     
         48 . The kit of  claim 44 , wherein the administration to the patient occurs between about 1 hour prior to consuming food to about 2 hours after consuming food.  
     
     
         49 . The kit of  claim 48 , wherein the administration to the patient is substantially at the same time as the consumption of the food.  
     
     
         50 . The kit of  claim 48 , wherein the administration to the patient is immediately after the consumption of food to up to about 1 hour after the consumption of food.  
     
     
         51 . The kit of  claim 44 , wherein the pharmaceutical composition is in a unit dosage form of a tablet.  
     
     
         52 . The kit of  claim 51 , wherein the tablet comprises about 100 mg to about 1800 mg of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate.  
     
     
         53 . The kit of  claim 52 , wherein the tablet comprises about 300 mg of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate, and the therapeutically effective amount is about 300 mg to about 900 mg.