DICLOFENAC: A Review on Its Synthesis, Mechanism of Action, Pharmacokinetics, Prospect and Environmental Impact

Abstract

Diclofenac, potent a nonsteroidal anti-innammatory drug, used in the treatment of innammation, pain and fever associated with a wide range of disease condition. This review article focuses the synthesis, mechanism of action, pharmacokinetics and derivatives of diclofenac and also highlights advances in the possible use of diclofenac in treating other condition outside its current clinical therapeutic use as an analgesic, anti-innammatory and antipyretic agent as well the prospect of drug repurposing of diclofenac for treatment of disease like cancer. It further highlights the adverse eeect of the drug as an emerging contaminant in the environment. Diclofenac acts by inhibition of COX enzymes and subsequently reduces the synthesis of prostaglandins, the predominant prostanoid produced in innammatory processes. Diclofenac is primarily metabolized in the liver and is eliminated in the urine and bile as conjugates of diclofenac and its metabolites. Despite its eeectiveness in management of pain, innammation and fever, there are reports of adverse gastrointestinal, cardiovascular and renal eeect resulting from its systemic use, suggesting the need for more research on its drug modiication in order to reduce or eliminate the adverse eeects. Research suggests that diclofenac has antimicrobial, anticancer and neuroprotective property. As an anticancer agent, research suggests diclofenac exhibit anti-proliferative and apoptosis mediating property. Diclofenac arrest cell cycle, thus preventing proliferation of neural stem cells, glioblastomas, ovarian cells, osteoblasts, human lymphatic endothelial cells, and vascular smooth muscle cells and induces apoptosis of neuroblastoma cell, this project this drug as a novel prospective anticancer agent. However, its adverse environmental eeects as an emergent contaminant still remains a source of concern.