Eprosartan Mesylate

Sprue-like enteropathy (SE) related to olmesartan use was first reported in 2012. In 2017, the manufacturer of Benicar paid $300 million for 2300 claims for olmesartan-related SE.

A study in 2019 suggested that SE was related to olmesartan and with the possibility of angiotensin receptor blocker (ARB) class effect. To further characterize this condition, our group examined reports of ARB-related SE to Food and Drug Administration Adverse Event Reporting System (FAERS).

All reports of ARB-related SE from January 2017 to December 2021 were downloaded from the FAERS database. Gastrointestinal adverse events including SE were reviewed. Reporter categories included physicians, pharmacists, other health care professionals, consumers, and attorneys.

A total of 106 590 reports of ARB-related adverse effects were analyzed. Sprue-like enteropathy was identified in 4337 cases (4.1% of total reports). Of these, 4240 cases (98.0%) of ARB-related SE were reported in patients using products with olmesartan, and 97 cases of SE were reported for all other ARBs (eprosartan, losartan, telmisartan, irbesartan, valsartan, and candesartan). Reports of olmesartan-related SE increased rapidly in 2017, continued at a high rate in 2018 and 2019, and essentially stopped in 2020 and 2021.

Reports to FAERS for ARB-related SE are mostly related to olmesartan. There was a steep decline in reports of olmesartan-related SE following the lawsuit with potential of lawyer interference. There are reports of SE related to ARBs other than olmesartan, with increased physician awareness and the potential to discover a class effect with future studies.

The global prevalence of obesity-related systemic disorders, including non-alcoholic fatty liver disease (NAFLD), and cancers are rapidly rising. Several of these disorders involve peroxisome proliferator-activated receptors (PPARs) as one of the key cell signaling pathways. PPARs are nuclear receptors that play a central role in lipid metabolism and glucose homeostasis. They can activate or suppress the genes responsible for inflammation, adipogenesis, and energy balance, making them promising therapeutic targets for treating metabolic disorders. In this study, an attempt has been made to screen novel PPAR pan-agonists from the ZINC database targeting the three PPAR family of receptors (α, γ, β/δ), using molecular docking and molecular dynamics (MD) simulations. The top scoring five ligands with strong binding affinity against all the three PPAR isoforms were eprosartan, canagliflozin, pralatrexate, sacubitril, olaparib. The ADMET analysis was performed to assess the pharmacokinetic profile of the top 5 molecules. On the basis of ADMET analysis, the top ligand was subjected to MD simulations, and compared with lanifibranor (reference PPAR pan-agonist). Comparatively, the top-scoring ligand showed better protein-ligand complex (PLC) stability with all the PPARs (α, γ, β/δ). When experimentally tested in in vitro cell culture model of NAFLD, eprosartan showed dose dependent decrease in lipid accumulation and oxidative damage. These outcomes suggest potential PPAR pan-agonist molecules for further experimental validation and pharmacological development, towards treatment of PPAR-mediated metabolic disorders.