To enhance the activity of amantadine against HCV, its amide prodrugs with thiazolidine-4-carboxylic acid derivatives (6-9) and bile acids (10 and 11) were designed and synthesized. In vitro kinetic stability of amide prodrugs 8 and 10 were investigated in aqueous buffer solution with variable pH values (1.2, 4.5. 6.8, 7.4. 8.0) and in biological fluids of 90% human plasma and rat liver homogenate at 37°C. In vivo release of the parent drug from these prodrug was investigated in mice with the thioazolidine-4-carboxylic acid amide 8 as representative of these delivery systems. Results from the in vivo distribution study indicated that the level of amantadine increased significantly in liver from 8 when compared to amantadine itself. The study suggested the synthesized delivery systems is promising carrier to enhance the hepatic bioavailability of amantadine.
Research Department	
              
          Research Journal	
              Digest Journal of Nanomaterials and Biostructures
          Research Publisher	
              the Academy of Romanian Scientists
          Research Rank	
              1
          Research Vol	
              Vol. 6, No. 4
          Research Website	
              http://www.chalcogen.infim.ro/1675_Fadl.pdf
          Research Year	
              2011
          Research Member	
          
      Research Abstract