Title:Synthesis, Biological Evaluation and Pharmacokinetic Studies of Mefenamic Acid - N-Hydroxymethylsuccinimide Ester Prodrug as Safer NSAID
VOLUME: 12 ISSUE: 6
Author(s):Asif Husain, Priyanka Ahuja, Aftab Ahmad and Shah A. Khan
Affiliation:Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi-110062, India.
Keywords:Ester prodrug, mefenamic acid, N-hydroxymethylsuccinimide, pharmacokinetics.
Abstract:Background: Non steroidal anti-inflammatory drugs are the most widely prescribed drugs
to manage pain and inflammatory conditions, but their long term use is associated with gastrointestinal
toxicity.
Objectives: The study aimed to synthesize an ester-based prodrug of a non steroidal anti-inflammatory
agent, mefenamic acid in order to improve the therapeutic index vis a vis to overcome the side effects
such as gastrointestinal irritation and bleeding associated with the use of mefenamic acid.
Methods: The ester prodrug (MA-NH) was prepared by condensing mefenamic acid with N-hydroxymethylsuccinimide in
the presence of Phosphorus oxychloride. The pharmacokinetic profile, including stability and release of mefenamic acid
and N-hydroxymethylsuccinimide from the ester prodrug (MA-NH) was studied by RP- HPLC in acidic medium (pH 1.2),
basic medium (pH 7.4), 80 % v/v human plasma, 10 % w/v rat intestinal homogenate and 10 % w/v rat liver homogenate
(pH 7.4).
Results: The chemical structure of the title compound was characterized by using modern spectroscopic techniques. The
prodrug was found to be stable in acid medium, but it hydrolyzed and released sufficient quantities of the drug in alkaline
medium. The prodrug produced lesser number of ulcers and showed improved analgesic and anti-inflammatory activity as
compared to the parent drug.
Conclusion: The results indicate that the synthesized prodrug (MA-NH) is better in terms of analgesic and antiinflammatory
activities and with less GI toxicity than the parent drug.
