title: Synthesis, kinetics and pharmacological evaluation of mefenamic acid mutual prodrug.
abstract: A novel mutual prodrug (MA-P) consisting of mefenamic acid (MA) and paracetamol (P) has been synthesized as a gastrosparing NSAID, devoid of ulcerogenic side effects. The structure of synthesized drug was confirmed by elemental analysis, infrared spectroscopy, 1H NMR spectroscopy and mass spectrometry.The kinetics of ester hydrolysis was studied by HPLC at pH 2, pH 7.4 as well as in human plasma. The pharmacological activities (anti-inflammatory, analgesic and ulcerogenic) were evaluated for the synthesized drug. The ulcerogenic reduction in terms of gastric wall mucosa, hexosamine and total proteins were also measured in glandular stomach of rats. The results indicated that MA-P ester has better ulcer index than the parent drug.
authors.affiliation: Institute of Pharmaceutical Research, GLA University, Mathura, U.P. 281406, India. kamal0603@gmail.com
authors.forename: Kamal
authors.initials: K
authors.lastname: Shah
authors.forename: Sushant K
authors.initials: SK
authors.lastname: Shrivastava
authors.forename: Pradeep
authors.initials: P
authors.lastname: Mishra
mesh_terms: D000082:Acetaminophen / Q000737:chemistry* / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008528:Mefenamic Acid / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013276:Stomach Ulcer / Q000139:chemically induced
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D011355:Prodrugs; D000082:Acetaminophen; D008528:Mefenamic Acid; D002351:Carrageenan