Colon-specific prodrugs of 4-aminosalicylic acid for inflammatory bowel disease.
Despite the advent of biological products, such as anti-tumor necrosis factor-α monoclonal antibodies (infliximab and adalimumab), for treatment of moderate to severe cases of inflammatory bowel disease (IBD), most patients depend upon aminosalicylates as the conventional treatment option. In recent years, the increased knowledge of complex pathophysiological processes underlying IBD has resulted in development of a number of newer pharmaceutical agents like low-molecular-weight heparin, omega-3 fatty acids, probiotics and innovative formulations such as high-dose, once-daily multi-matrix mesalamine, which are designed to minimize the inflammatory process through inhibition of different targets. Optimization of delivery of existing drugs to the colon using the prodrug approach is another attractive alternative that has been utilized and commercialized for 5-aminosalicylic acid (ASA) in the form of sulfasalazine, balsalazide, olsalazine and ipsalazine, but rarely for its positional isomer 4-ASA - a well-established antitubercular drug that is twice as potent as 5-ASA against IBD, and more specifically, ulcerative colitis. The present review focuses on the complete profile of 4-ASA and its advantages over 5-ASA and colon-targeting prodrugs reported so far for the management of IBD. The review also emphasizes the need for reappraisal of this promising but unexplored entity as a potential treatment option for IBD.
Suneela S Dhaneshwar, Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune-411 038, Maharashtra, India.
Suneela S
SS
Dhaneshwar
D010131:Aminosalicylic Acid / Q000494:pharmacology*; D000636:Aminosalicylic Acids / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003106:Colon / Q000187:drug effects*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D019804:Mesalamine / Q000627:therapeutic use; D010659:Phenylhydrazines / Q000627:therapeutic use; D011355:Prodrugs / Q000494:pharmacology*; D012460:Sulfasalazine / Q000627:therapeutic use
D000636:Aminosalicylic Acids; D015525:Fatty Acids, Omega-3; D006495:Heparin, Low-Molecular-Weight; D010659:Phenylhydrazines; D011355:Prodrugs; D012460:Sulfasalazine; C038636:ipsalazide; D019804:Mesalamine; D010131:Aminosalicylic Acid; C038637:balsalazide; C032587:olsalazine
2,4,6-trinitrobenzene sulphonic acid; 4-Aminosalicylic acid; 5-Aminosalicylic acid; Colon-specific prodrug; Experimental colitis; Inflammatory bowel disease; Sulfasalazine; Ulcerative colitis