Ketoconazole enantiomer in humans

Abstract

Treatment of patients with the 2S, 4R ketoconazole enantiomer or its pharmaceutically acceptable salts, and solvates is useful for reducing systemic inflammation and cholesterol levels and improving glycemic control.

What is claimed is: 
     
         1 . A method of treating a patient that is diabetic, non-diabetic with elevated cortisol, or non-diabetic with elevated cholesterol comprising
 co-administering a 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor and a composition to said patient, wherein the composition comprises a therapeutically effective amount of the 2S,4R ketoconazole enantiomer, wherein the ketoconazole content of the composition comprises at least 98% of the 2S,4R ketoconazole enantiomer and less than 2% of the 2R,4S ketoconazole enantiomer.   
     
     
         2 . The method of  claim 1 , wherein administration of the HMG-CoA reductase inhibitor is contraindicated in the patient in the absence of administration of the 2S,4R ketoconazole enantiomer. 
     
     
         3 . The method of  claim 1 , wherein the HMG-CoA reductase inhibitor is selected from the group consisting of lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin, itavastatin, ZD-4522, and rivastatin. 
     
     
         4 . The method of  claim 1 , wherein the patient is non-diabetic with elevated Cortisol. 
     
     
         5 . The method of  claim 1 , wherein the HMG CoA reductase inhibitor is a cholesterol-lowering HMG CoA reductase inhibitor. 
     
     
         6 . The method of  claim 1 , wherein the patient is non-diabetic with elevated cholesterol. 
     
     
         7 . The method of  claim 1 , wherein the therapeutically effective amount of the 2S,4R ketoconazole enantiomer is a daily dose of from 100 mg to 600 mg. 
     
     
         8 . The method of  claim 1 , wherein the therapeutically effective amount of the 2S,4R ketoconazole enantiomer is a daily dose of 400 mg. 
     
     
         9 . The method of  claim 1 , wherein the composition is free of the 2R,4S ketoconazole enantiomer. 
     
     
         10 . The method of  claim 1 , wherein the HMG-CoA reductase inhibitor is atorvastatin. 
     
     
         11 . The method of  claim 10 , wherein the Cmax of the total of atorvastatin, 2-hydroxy atorvastatin and 4-hydroxy atorvastatin is reduced relative to administration of atorvastatin in the absence of administration of the 2S,4R ketoconazole enantiomer. 
     
     
         12 . The method of  claim 10 , wherein the AUC of the total of atorvastatin, 2-hydroxy atorvastatin and 4-hydroxy atorvastatin is increased relative to administration of atorvastatin in the absence of administration of the 2S,4R ketoconazole enantiomer.