جستجوی مقالات مرتبط با کلیدواژه « ezetimibe » در نشریات گروه « پزشکی »

One of the most potentially hazardous diseases, prostate cancer has a high morbidity and mortality rate. Polymeric matrix drug-eluting implants have become widely employed, and modeling their behavior is becoming more and more prominent. It is always difficult to achieve effective drug delivery and release of it into specific tumor sites. One of the most significant purposes of this investigation, is the enhancement of the anticancer effects of prostate cancer treatment by co-delivering anticancer multi-drugs with PU-PCL films. The films were recognized utilizing SEM  (scanning electron microscopy) while the material was being characterized. In addition, the MTT assay and flow cytometry (Annexin V/PI staining) have been employed to assess cell viability at various times. A dialysis approach was used to investigate the drug release characteristics of DOX and Ezetimibe in films in vitro for 5 days. To optimize pharmacokinetic profiles and reduce systemic toxicity induced by drugs, we loaded polymeric PU-PCL films with ezetimibe (EZ) and doxorubicin (DOX). Co-delivery of EZ and DOX via film-carrier demonstrated improved anticancer effects when compared to free drug delivery. The co-delivery of DOX and EZ drugs by PU-PCL films improved anticancer effects while reducing systemic toxicity, suggesting clinical usage of drug-resistant prostate cancer therapy.

Drug repurposing is an effective strategy for identifying the use of approved drugs for new therapeutic purposes. This strategy has received particular attention in the development of cancer chemotherapy. Considering that a growing body of evidence suggesting the cholesterol-lowering drug ezetimibe (EZ) may prevent the progression of prostate cancer, we investigated the effect of EZ alone and in combination with doxorubicin (DOX) on prostate cancer treatment.

In this study, DOX and EZ were encapsulated within a PCL-based biodegradable nanoparticle. The physicochemical properties of drug containing nanoparticle based on PCL-PEG-PCL triblock copolymer (PCEC) have been exactly determined. The encapsulation efficiency and release behavior of DOX and EZ were also studied at two different pHs and temperatures.

The average size of nanoparticles (NPs) observed by field emission scanning electron microscopy (FE-SEM) was around 82±23.80 nm, 59.7±18.7 nm, and 67.6±23.8 nm for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively, which had a spherical morphology. In addition, DLS measurement showed a monomodal size distribution of around 319.9, 166.8, and 203 nm hydrodynamic diameters and negative zeta potential (-30.3, -6.14, and -43.8) mV for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively. The drugs were released from the NPs sustainably in a pH and temperature-dependent manner. Based on the MTT assay results, PCEC copolymer exhibited negligible cytotoxicity on the PC3 cell line. Therefore, PCEC was a biocompatible and suitable nano-vehicle for this study. The cytotoxicity of the DOX-EZ-loaded NPs on the PC3 cell line was higher than that of NPs loaded with single drugs. All the data confirmed the synergistic effect of EZ in combination with DOX as an anticancer drug. Furthermore, fluorescent microscopy and DAPI staining were performed to show the cellular uptake, and morphological changes-induced apoptosis of treated cells.

Overall, the data from the experiments represented the successful preparation of the nanocarriers with high encapsulation efficacy. The designed nanocarriers could serve as an ideal candidate for combination therapy of cancer. The results corroborated each other and presented successful EZ and DOX formulations containing PCEC NPs and their efficiency in treating prostate cancer.

Gentamicin, despite its beneficial effects, has significant nephrotoxic effects that are observed in 20% of the patients. Ezetimibe is recognized as an inhibitor of cholesterol absorption.

The present study aimed to investigate the histopathological effects of ezetimibe on gentamicin-induced kidney damage.

Twenty male Wistar rats were randomly divided into five groups and treated as the following; group 1 (normal group), group 2 [gentamicin group, daily 80 mg/kg, intraperitoneal (i.p.) for seven days], group 3-5 (gentamicin 80 + ezetimibe at doses of 2.5, 12.5, and 37.5 mg/kg, respectively). Kidney sections were examined for histopathological parameters including vacuolization of the tubular renal cells, degeneration, necrosis, flattening of the tubular cells and debris in the tubular lumen.

Gentamicin injection significantly induced histopathological alterations (P< 0.05). Ezetimibe therapy significantly decreased the levels of vacuolization, degeneration, necrosis, flattening of the tubular cells and debris in the nephrotoxic rats (P< 0.05).

The results illustrated that treatment with ezetimibe can improve kidney damage caused by gentamicin injection.

The monotherapies of statin and ezetimibe had not successfully achieved their objectives in the management of lipid levels of dyslipidemia patients. We aimed to compare the effects of combined low-dose simvastatin and ezetimibe versus high-dose statin on the lipid-lowering treatment of dyslipidemia patients. We searched five databases published before May 2018, namely PubMed, EMBASE, Cochrane, Web of Science, and Clinicaltrials.gov. Completely published randomized controlled trials (RCTs) comparing the effect of high-dose statin (S) with ezetimibe/simvastatin (10/10 mg; E/S) on the management of dyslipidemia patients were included. A total of ten RCTs met the inclusion criteria, including 1,624 patients (E/S:691, S:933). Six out-comes underwent pooled analysis, including weighted mean difference (WMD) from baseline in total choles-terol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high sensitivity C-reactive protein (hs-CRP), triglyceride (TG), and non-high-density lipoprotein cholesterol (non-HDL-C). No significant gap was found between high-dose statin and ezetimibe/simvastatin (10/10 mg) in LDL-C (-1.55; 95% confidence interval [CI]:-4.42~1.31, P=0 .29), HDL-C (1.05; 95%CI:-0.21~2.3, P=0 .1), TG (4.03; 95%CI:-4.53~12.58, P=0.36), and hs-CRP (0.14; 95%CI:-0.50~0.78, P=0.67). However, there was significant difference found between the two lipid-lowering treatments in TC (-0.45; 95%CI:-9.07~-0.83, P=0.02) and non-HDL-C (-4.97; 95%CI -8.46~-1.49, P=0.005). Ezetimibe co-administered with simvastatin (10 mg) and high-dose statin monotherapy may show similar effects in reducing LDL-C, TG, and hs-CRP levels and in increasing HDL-C levels. However, the results suggest that there was greater TC and non-HDL-C lowering through high-dose statin monotherapy as compared with ezetimibe/simvastatin co-administration.

Ezetimide belongs to a class of lipid lowering compounds that selectively inhibits intestinal absorption of cholesterol and related phytosterols. The purpose of this study is to establish a reliable and quick method for the assignment of ezetimibe in tablets form by high performance liquid chromatography with ultraviolet detection (HPLC-UV). A rapid and sensitive HPLC method has been developed for determination of ezetimibe in tablets formulation. Mobile phase was composed of acetonitrile-ammonium acetate (10 mM, pH 3.0), 75:25 (v/v) with a flow rate of 1 ml/min. The eluted peaks were detected by a UV detector was set at wavelength of 240 nm. The method results in excellent separation with good resolution of analyte. Standard curves were linear (r = 0.996) over the wide ezetimibe concentration range of 10-60.0 µg mL-1 with acceptable accuracy and precision. The limits of detection (LOD) and quantitation (LOQ) of the method were 5 and 10 µg/ml, respectively. The average drug recovery was 95.3% throughout the linear concentration range. Statistical assessment of various in vitro dissolution parameters and assay results was also conducted to establish if there were any significant difference among them. The validated HPLC method has been used successfully to study ezetimibe. Due to simplicity, rapidity and accuracy of the method, we believe that the method will be useful for routine quality control analysis.

Two simple, precise and accurate multivariate calibration methods, partial least square (PLS) and principal component regression (PCR) have been applied for the simultaneous determination and dissolution profile evaluation of atorvastatin (ATV) and ezetimibe (EZT) in their binary mixtures and commercial tablets. Due to the closely overlapping spectral bands of the mentioned drugs, simultaneous determination without previous separation is not possible by conventional spectrophotometric methods. In the proposed methods (PLS and PCR) determination of chemicals was performed by the use of a full-spectrum multivariate calibration method.
The experimental calibration matrix was designed orthogonally with 16 samples composed of different mixtures of both compounds in related mediums. The simultaneous determination of ATV and EZT was accomplished in mixtures through recording the absorption spectra within a range of 210 to 300 nm.
The concentration of ATV and EZT were considered in the linear range, between 8 to 14 µg.ml-1. The specificity of the methods was evaluated by analyzing laboratory prepared mixtures of the mentioned drugs in specific proportions.
The applied methods were successfully employed in simultaneous spectrophotometric determination and dissolution profile evaluation of ATV and EZT in their prepared mixtures and pharmaceutical formulation.

This paper describes a simple, precise and accurate RP-HPLC method for simultaneous estimation of atorvastatin and ezetimibe in plasma. The chromatographic separation of the drugs were performed on an X-Terra C (4.6 x 150 mm, 3.5 m), with phosphate buffer [pH 3.5 with Ortho Phosphoric Acid] – acetonitrile 40:60 (v/v) as mobile phase. The detection was performed at 235 nm. The flow rate was maintained at 1.2 mL/min. The run time was 8.0 min. The accuracy and reliability of the method was assessed by evaluation of linearity (5-25 μg/mL for both atorvastatin calcium and ezetimibe), precision (intra-day RSD 0.57 % and inter-day RSD 0.02 % for atorvastatin calcium and intra-day RSD 0.56 % and inter day RSD 0.1 % for ezetimibe), accuracy (100.08- 100.84 % for atorvastatin calcium and 100.56- 101.00 % for ezetimibe), and specificity, in accordance with ICH guidelines. The LLOQ obtained by the proposed method were 1.294 and 1.384 μg/mL for atorvastatin and ezetimibe respectively. Overall the proposed method was found to be suitable and accurate for the quantitative determination in plasma. The method was effectively separated the drug from plasma.

Combination therapy plays an important role in the management of cardiovascular disease (CVD). The aim of this experiment was to study the influence of garlic combined with ezetimibe on lipid profile as well as intestinal Niemann-Pick C1-like 1 (NPC1L1) expression in normal and hypercholesterolemic mice. A total of 40 mice were randomly divided into five groups: Group 1: hypercholesterolemic group (received 2% w/w cholesterol + 0.5% w/w cholic acid in their diet), Group 2: garlic group (hypercholesterolemic diet + 4% w/w garlic extract), Group 3: ezetimibe group (hypercholesterolemic diet + 0.005% w/w ezetimibe), Group 4: combination group (hypercholesterolemic diet + 0.005% w/w ezetimibe + 4% w/w garlic) and Group 5: control (chow only). Serum low-density lipoprotein-cholesterol (LDL-C) and total cholesterol (TC) levels were significantly decreased in ezetimibe, garlic (both P < 0.05), and combination groups (P < 0.001). Also, triglycerides and very low-density lipoprotein-cholesterol (VLDL-C) were significantly lower in garlic and combination groups (P < 0.05). Liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were also significantly decreased in garlic, ezetimibe (both P < 0.05) and combination groups (P < 0.001) in comparison with hypercholesterolemic animals. Analysis of semi quantitative RT-PCR results showed that the levels of NPC1L1 was also significantly less (P < 0.01) in the garlic, ezetimibe, and combination groups (P < 0.001) compared with the controls. Based on the results, the combination of garlic and ezetimibe can lower serum lipids and liver enzymes more effectively in hypercholesterolemic mice. This experiment revealed that a possible mechanism for the beneficial effects of garlic and ezetimibe combination in lowering plasma LDL-C and TC is inhibition of intestinal cholesterol absorption. More research might be necessary to determine the efficacy and the exact mechanism of this co-administration.

A simple stability indicating reverse phase liquid chromatographic method was developed for the simultaneous determination of rosuvastatin and ezetimibe in pharmaceutical formulations. Best chromatographic response was achieved with C18 column (250 X 4.6 mm, 5μm) with photo diode array (PDA) detector. The mobile phase was composed of a mixture of sodium acetate buffer (pH 4.0) and acetonitrile (30:70, %v/v) with a flow rate of 1.2 mL/min. (UV detection at 254 nm). Rosuvastatin and ezetimibe were subjected to stress conditions of degradation and the method was validated as per ICH guidelines. The method shows linearity over a concentration range of 0.5–250 μg/ml for both rosuvastatin (r2 = 0.9993) and ezetimibe (r2 = 0.9996). Both the drugs are highly sensitive towards alkaline conditions in comparison to other stress conditions. The proposed method can be successfully applied to perform long-term and accelerated stability studies for the simultaneous determination of rosuvastatin and ezetimibe in pharmaceutical formulations.

Ezetimibe inhibits the resorption of dietary and biliary cholesterol in the small intestine and decreases insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). Acarbose has been used in type 2 diabetes mellitus and metabolic syndrome. This study aims to compare the therapeutic effects of ezetimibe and acarbosein decreasing liver transaminase levels in patients with NAFLD. This was a single center, double-blind, parallel-group study conducted at Bu-Ali Sina Hospital, Qazvin, Iran. In this trial, we enrolled, by simple randomization, a total of 62 patients diagnosed with NASH. There were 29 patients treated with ezetimibe and 33 who were treated with acarbose over a ten-week period. Ezetimibe treatment significantly reduced ALT, AST, triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-sensitivity C-reactive protein (hsCRP), and serum insulin levels and the insulin resistance homeostasis model assessment (HOMA-IR) index compared to patients treated with acarbose (p)Both ezetimibe and acarbose improved metabolic and biochemical abnormalities in patients with NASH, however these effects were more prominent with ezetimibe.

This randomized, double blind trial was designed to compare the efficacy and safety of ezetimibe, a new cholesterol-lowering agent with atorvastatin (Lipitor), a potent cholesterolinhibitor derivative.

Between September 2004 and March 2005, a total of 120 hyperlipidemic patients, aged 28-80 years, were randomized to receive ezetimibe 10 mg or atorvastatin 10 mg orally daily for 8 weeks after a 4-week washout phase and diet on NCEP step II. Mean changes of serum lipoproteins after 4 and 8 weeks of drug therapy were measured and compared in both groups of patients.

Ezetimibe reduced LDLc and total cholesterol by a mean of 27% and 16% compared with 32% and 24% for atorvastatin, respectively. The difference was not statistically significant.

Ezetimibe and atorvastatin both reduced LDLc and TC with no statistically significant difference