title: Optimized prodrug approach: a means for achieving enhanced anti-inflammatory potential in experimentally induced colitis.
abstract: In the present study, prodrug of ketoprofen was synthesized and evaluated in vitro to optimize the prodrug, and in vivo to observe the reduction in gastrointestinal disturbance and enhanced colonic anti- inflammatory potential for the prodrug. The prodrug was synthesized by coupling ketoprofen with L-glycine (KET-GLY). In vitro reversion of KET-GLY to ketoprofen was carried out in different pHs and in pH 6.8 containing optimized rat fecal material. In vivo healing potential of KET-GLY was evaluated in acetic acid-induced experimental colitis model. In vitro reversion studies suggested that KET-GLY remained intact in stomach but released the free drug at pH 6.8 containing fresh rat fecal material, where the colonic microfloral enzymes (amidase) hydrolyzed the KET-GLY amide linkage, releasing the free drug. In vivo evaluation indicated KET-GLY to be less toxic in stomach, with enhanced anti-inflammatory potential in the colonic region. These findings suggested KET-GLY to be better in action compared with the parent drug.
authors: Department of Pharmaceutics, Rajiv Academy for Pharmacy, Uttar Pradesh, India. philipanil23@yahoo.co.in
authors: Anil K
authors: AK
authors: Philip
authors: Sunny
authors: S
authors: Dabas
authors: Kamla
authors: K
authors: Pathak
mesh_terms: D019342:Acetic Acid / Q000009:adverse effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D005998:Glycine / Q000008:administration & dosage* / Q000737:chemistry; D007660:Ketoprofen / Q000008:administration & dosage* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D012460:Sulfasalazine / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D012460:Sulfasalazine; D007660:Ketoprofen; D019342:Acetic Acid; D005998:Glycine