How to cite this article: Komesli Y, Karasulu E. Evaluation of anti-inflammatory, immunomodulatory effects and celiac-like side effect of olmesartan medoxomil as a vitamin D receptor agonist and angiotensin II receptor blocker.
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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 drug and to enhance bioavailability. In this study, an artificial hypertension model was established with 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. 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 and 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.
Plasma concentrations of drug depend on the frequency of administration. In conventional drug release, the blood concentration of the drug increases, reaches a peak and falls after the drug administration. For these reasons, we plan to work responsive systems in our study. We have examined the response of different drug content of the polymeric tablets to the ultrasound. Polymeric controlled drug delivery systems were used to obtain controlled drug delivery. In this study, the relationship between the release rate constants, ultrasound and drug contents were investigated. It is found that the ultrasound has a very important effect on the release of drug and increases drug release clearly. The intensive works on responsive implantable polymeric drug systems had begun in 1980's. These systems are categorized in two different groups:1.
ORIGINAL RESEARCH ABSTRACTIn this study, the controlled release tablet of diltiazem hydrochloride was developed. The controlled release tablets were prepared with ethyl cellulose by changing the ratio of diltiazem hydrochloride and the in vitro release studies were carried out by using an ultrasonic water bath. According to release results, a new equation was developed that can be used to estimate the release of drug as a function of time and drug content in the formulation. In addition, the effect of ultrasound on the release of diltiazem hydrochloride from controlled release dosage forms and relationships between release rate constants and drug contents were investigated. This study showed that the developed equation can successfully be used to estimate the effect of ultrasound on the release of drug from the formulations prepared with different concentrations of diltiazem hydrochloride. It was concluded that ultrasound has a very important effect on the release of drug and increases drug release obviously.
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