Comparison of Pharmacodynamics and Celiac Effects of Olmesartan Medoxomil Formulations by using Olmesartan-induced Celiac-rat-model

Komesli Y., Ergur B. U. , KARASULU E.

CURRENT DRUG DELIVERY, vol.18, no.10, pp.1480-1490, 2021 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 18 Issue: 10
  • Publication Date: 2021
  • Doi Number: 10.2174/1567201818666210322144631
  • Title of Journal : CURRENT DRUG DELIVERY
  • Page Numbers: pp.1480-1490
  • Keywords: Hypertension, olmesartan medoxomil, pharmacodynamics, olmesartan-induced celiac rat model, enteropathy, diar-rhea, SMEDDS, GLUTEN-SENSITIVE ENTEROPATHY, DISEASE, PHARMACOKINETICS, PATHOGENESIS, COMBINATION, DIAGNOSIS, TOXICITY, IL-15, CELLS, MICE


Olmesartan Medoxomil (OM) is an angiotensin receptor blocker and has the adverse effect of celiac like enteropathy which was accepted by the FDA in 2013. This disease is characterized by severe diarrhea, weight loss and enteropathy. Although there are many case reports associated with olmesartan-related enteropathy in humans, it has not been described in a long-term animal model study so far. We developed a self-microemulsifying drug delivery system (OM-SMEDDS) in our previous study to reduce this side effect of the drug and to enhance bioavailability. In this study, an artificial hypertension model was established with a dose of 185 mu mol /kg L-NAME (N omega-nitro-L-arginine methyl ester) twice in a day intraperitoneally in Wistar albino rats. To determine and compare side effects, the OM-Suspension and OM-SMEDDS were administered at 1.3 mg/kg therapeutic dose during one-month period to the rats. Tension of rats was recorded by measuring from their tails with non invasive blood pressure system. We observed celiac like enteropathy findings like villous atrophy and intraepithelial lymphocytosis and clinical changes like weight loss and severe diarrhea after the treatment with OM-Suspension during one-month experiment. It was also observed that the antihypertensive efficacy of the OM-SMEDDS formulation was higher than the suspension during the experiment, which did not cause enteropathy, diarrhea and weight loss by reducing intestinal exposure. Hereby, we evaluated the side effects of two different pharmaceutical forms by designing a sustainable and reproducible celiac rat model that can be induced with olmesartan medoxomil.