Title:Comparison of Pharmacodynamics and Celiac Effects of Olmesartan Medoxomil Formulations by using Olmesartan-induced Celiac-rat-model
Volume: 18
Issue: 10
Author(s): Yelda Komesli*, Bekir Ugur Ergur and Ercument Karasulu
Affiliation:
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Altinbas University, Istanbul,Turkey
Keywords:
Hypertension, olmesartan medoxomil, pharmacodynamics, olmesartan-induced celiac rat model, enteropathy, diarrhea, SMEDDS.
Abstract:
Introduction: 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.
Aim: 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.
Methods: In this study, an artificial hypertension model was established with a dose of 185 μmol
/kg L-NAME (N ω-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.
Results: 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.
Conclusion: 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.
