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BMC Pharmacology & Toxicology Sep 2022Hypolipidemic agents have been shown to be helpful in the primary and secondary prevention of cardiovascular disease. Most often, statins are prescribed to treat...
BACKGROUND
Hypolipidemic agents have been shown to be helpful in the primary and secondary prevention of cardiovascular disease. Most often, statins are prescribed to treat hyperlipidemia. There are a number of statins available in the market today, but atorvastatin is the most widely prescribed. It is essential that the drugs should have the appropriate amount of active pharmaceutical ingredient and meet the necessary physical properties. The main purpose of the study was to evaluate the quality of different marketed brands of atorvastatin calcium tablets available in Saudi Arabia.
METHODS
In this study, innovator product coded as (AS-1) and five generics brands (coded as AS-2 to AS-6) of atorvastatin tablets 20 mg available in Saudi Arabia were evaluated for in vitro dissolution test, weight variations, friability and hardness tests. The analysis of drug was carried out by "high-performance liquid chromatography" (HPLC) method using C column (4.6 × 150 mm, 5 μm). The mobile phase was consisted of acetonitrile and HPLC water (pH 2.1, adjusted with orthophosphoric acid) in ratio of 52:48 v/v, the flow rate was 1.0 ml/min. Atorvastatin was detected at a wavelength of 254 nm.
RESULTS
According to the results of the dissolution study, the investigated products released more than 90% of atorvastatin in 15 min. Within 60 min, the brands AS-1, AS-3, AS-5, and AS-6 depicted nearly 100% atorvastatin release, while the brand AS-2 displayed 91.69% drug release. According to our findings, the investigated atorvastatin innovator (AS-1) and generic brands such as AS-2 to AS-6 were of good pharmaceutical quality.
CONCLUSIONS
All generic brands of atorvastatin tablets available in the Saudi Arabian market met the pharmacopoeia's consistency checks such as weight variation, friability, hardness and in vitro dissolution. Hence, focusing on their in vitro release properties, it was determined that these brands could be used interchangeably.
Topics: Atorvastatin; Drugs, Generic; Glycolates; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quality Control; Saudi Arabia; Tablets
PubMed: 36100946
DOI: 10.1186/s40360-022-00598-y -
Arquivos Brasileiros de Cardiologia Oct 2021Metabolic syndrome is characterized by an array of comorbidities. During this syndrome, structural changes are observed in the cardiovascular system, especially vascular...
BACKGROUND
Metabolic syndrome is characterized by an array of comorbidities. During this syndrome, structural changes are observed in the cardiovascular system, especially vascular remodeling. One of the predisposing causes for these changes is chronic inflammation resulting from changes in the structure and composition of perivascular adipose tissue. Atorvastatin is effective in the treatment of dyslipidemias. However, its pleiotropic effects have not been completely understood. We hypothesize that metabolic syndrome may lead to vascular remodeling and that atorvastatin therapy may be able to attenuate this condition.
OBJECTIVES
To assess the effects of atorvastatin therapy on vascular remodeling in an experimental model of metabolic syndrome.
METHODS
Swiss mice received a control diet or a hyperglicemic diet for 18 weeks. After 14 weeks of diet, mice were treated with vehicle or atorvastatin (20mg/kg) during for 4 weeks. Nutritional and metabolic profiles were assessed by biochemical tests; moreover, a histological assessment of aorta structure was conducted, and cytokine levels were determined by the immunoenzyme assay. The acceptable level of significance for the results was set at p<0.05.
RESULTS
Hyperglicemic diet promoted the development of metabolic syndrome. It indeed culminated in hypertrophic remodeling of vascular smooth muscle and perivascular adipose tissue. Furthermore, there were increases in the levels of circulating TNF-α and IL-6 and in the perivascular adipose tissue. Atorvastatin therapy significantly reduced metabolic damages, vascular remodeling, and cytokine levels.
CONCLUSION
Atorvastatin attenuate metabolic damages associated with metabolic syndrome induced by hyperglycemic diet, in addition to attenuating vascular remodeling; both effects are associated with reduced levels of pro-inflammatory cytokines.
Topics: Adipose Tissue; Animals; Atorvastatin; Cytokines; Metabolic Syndrome; Mice; Vascular Remodeling
PubMed: 34161419
DOI: 10.36660/abc.20200322 -
Theranostics 2024: Meningeal lymphatic vessels (MLVs) are essential for the clearance of subdural hematoma (SDH). However, SDH impairs their drainage function, and the pathogenesis...
: Meningeal lymphatic vessels (MLVs) are essential for the clearance of subdural hematoma (SDH). However, SDH impairs their drainage function, and the pathogenesis remains unclear. Herein, we aimed to understand the pathological mechanisms of MLV dysfunction following SDH and to test whether atorvastatin, an effective drug for SDH clearance, improves meningeal lymphatic drainage (MLD). : We induced SDH models in rats by injecting autologous blood into the subdural space and evaluated MLD using Gadopentetate D, Evans blue, and CFSE-labeled erythrocytes. Whole-mount immunofluorescence and transmission electron microscopy were utilized to detect the morphology of MLVs. Phosphoproteomics, western blot, flow cytometry, and experiments were performed to investigate the molecular mechanisms underlying dysfunctional MLVs. : The basal MLVs were detected to have abundant valves and play an important role in draining subdural substances. Following SDH, these basal MLVs exhibited disrupted endothelial junctions and dilated lumen, leading to impaired MLD. Subsequent proteomics analysis of the meninges detected numerous dephosphorylated proteins, primarily enriched in the adherens junction, including significant dephosphorylation of ERK1/2 within the meningeal lymphatic endothelial cells (LECs). Subdural injection of the ERK1/2 kinase inhibitor PD98059 resulted in dilated basal MLVs and impaired MLD, resembling the dysfunctional MLVs observed in SDH. Moreover, inhibiting ERK1/2 signaling severely disrupted intercellular junctions between cultured LECs. Finally, atorvastatin was revealed to protect the structure of basal MLVs and accelerate MLD following SDH. However, these beneficial effects of atorvastatin were abolished when combined with PD98059. : Our findings demonstrate that SDH induces ERK1/2 dephosphorylation in meningeal LECs, leading to disrupted basal MLVs and impaired MLD. Additionally, we reveal a beneficial effect of atorvastatin in improving MLD.
Topics: Rats; Animals; Glymphatic System; Atorvastatin; Endothelial Cells; MAP Kinase Signaling System; Hematoma, Subdural; Lymphatic Vessels
PubMed: 38164141
DOI: 10.7150/thno.87633 -
Chemical & Pharmaceutical Bulletin Oct 2008The objective of the study is to formulate bilayer tablets consisting of atorvastatin calcium (AT) as an immediate release layer and nicotinic acid (NA) as an extended...
The objective of the study is to formulate bilayer tablets consisting of atorvastatin calcium (AT) as an immediate release layer and nicotinic acid (NA) as an extended release layer. The immediate release layer was prepared using super disintegrant croscarmellose sodium and extended release layer using hydroxypropylmethyl cellulose (HPMC K100M). Both the matrix and bilayer tablets were evaluated for hardness, friability, weight variation, thickness, and drug content uniformity and subjected to in vitro drug release studies. The amount of AT and NA released at different time intervals were estimated by HPLC method. The bilayer tablets showed no significant change either in physical appearance, drug content or in dissolution pattern after storing at 40 degrees C/75% relative humiding (RH) for 3 months. The release of the drug from the tablet was influenced by the polymer content and it was much evident from thermogravimetry/differential thermal analysis (TG/DTA) analysis. The results indicated that the bilayer tablets could be a potential dosage form for delivering AT and NA.
Topics: Atorvastatin; Carboxymethylcellulose Sodium; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Drug Combinations; Drug Incompatibility; Drug Stability; Drug Storage; Excipients; Hardness; Heptanoic Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypromellose Derivatives; Methylcellulose; Niacin; Pyrroles; Solubility; Tablets
PubMed: 18827389
DOI: 10.1248/cpb.56.1455 -
Trials Jan 2019Vitiligo is a chronic skin disorder presenting with depigmentation, the pathogenesis of which is complex but the autoimmune theory is now preferred. Multiple immunologic...
The Evaluation of Vitiligous lesions Repigmentation after the Administration of Atorvastatin calcium salt and Simvastatin-acid sodium salt in patients with active vitiligo (EVRAAS), a pilot study: study protocol for a randomized controlled trial.
BACKGROUND
Vitiligo is a chronic skin disorder presenting with depigmentation, the pathogenesis of which is complex but the autoimmune theory is now preferred. Multiple immunologic processes, including stimulation of the T-helper (Th)1 response, formation of autoreactive melanocyte-specific CD8 T lymphocytes, a decrease in the blood concentration of T regulatory (Treg) cells, and an increase in interleukin (IL)-17 and interferon (IFN) concentration, have been shown to contribute to vitiligo progression and maintenance. The aim of this study is to evaluate the influence of simvastatin and atorvastatin on vitiligous lesions in patients with nonsegmental vitiligo (NSV). According to available data, statins act through several immunological pathways, potentially reversing undesirable phenomena underlying autoimmune vitiligo pathogenesis.
METHODS/DESIGN
A study has been designed as a single-center, randomized, double-blind, placebo-controlled pilot study with the enrollment of at least 24 active NSV patients presenting with vitiligous lesions on both upper and lower limbs. The clinical effects of ointments containing 1% simvastatin-acid sodium salt or 1% atorvastatin calcium salt applied on a preselected limb will be assessed in comparison with vehicle ointment applied on the opposite limb. All study participants will undergo clinical evaluation using body surface area (BSA) and Vitiligo Area Scoring Index (VASI) scales at baseline and at weeks 4, 8, and 12 time points. A precise assessment of skin lesions will be performed using photographic documentation obtained during each study visit and processed with NIS-Elements software.
DISCUSSION
Currently available vitiligo topical therapeutic approaches including calcineurin inhibitors and corticosteroids remain poorly effective and are associated with either relatively high cost or potentially dangerous adverse effects. The clinical application of orally administrated statins, widely used as systemic cholesterol-lowering agents, in vitiligous patients has only been tested in two clinical trials; however, data on their potential usefulness is scarce. Moreover, due to a high risk of clinically significant toxicity, topical administration was recommended by researchers. This study is the first to evaluate safety and efficacy of the topical use of statins in patients presenting with NSV.
TRIAL REGISTRATION
Clinicaltrials.gov, NCT03247400 . Registered on 05 August 2017.
Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Atorvastatin; Double-Blind Method; Female; Humans; Male; Middle Aged; Ointments; Pilot Projects; Randomized Controlled Trials as Topic; Simvastatin; Skin Pigmentation; Vitiligo
PubMed: 30683146
DOI: 10.1186/s13063-018-3168-4 -
Anatolian Journal of Cardiology Oct 2015
Topics: Atorvastatin; Atrial Fibrillation; Coronary Artery Bypass; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Postoperative Complications
PubMed: 26828081
DOI: No ID Found -
Drug Design, Development and Therapy 2018Major cardiovascular risk factors, including hypertension and dyslipidemia, are often comorbidities, frequently leading to concurrent prescription of angiotensin... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Major cardiovascular risk factors, including hypertension and dyslipidemia, are often comorbidities, frequently leading to concurrent prescription of angiotensin receptor blockers and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins). The study's objective was to evaluate the effect of coadministration of fimasartan and atorvastatin on their pharmacokinetics (PKs).
SUBJECTS AND METHODS
In a randomized, open-label, three-period, six-sequence, crossover, multiple-dose study, 36 healthy subjects received 120 mg fimasartan, 40 mg atorvastatin, or both (based on their assigned sequence) once daily for 7 days in each period, with a 7-day washout between periods. Blood samples for the PK analysis of fimasartan, atorvastatin, and the 2-hydroxy atorvastatin metabolite were collected up to 48 h after the last dose.
RESULTS
The coadministration of fimasartan and atorvastatin was well tolerated and led to an increase in the peak concentration and area under the concentration-time curve at steady state of fimasartan by 2.18-fold (95% confidence interval [CI], 1.79-2.65) and 1.35-fold (95% CI, 1.26-1.43) and those of atorvastatin increased by 1.82-fold (95% CI, 1.51-2.18) and 1.12-fold (95% CI, 1.04-1.22), respectively.
CONCLUSION
Coadministration increased the systemic exposures of fimasartan and atorvastatin, but the clinical significance of this finding needs to be evaluated with respect to exposure responses and clinical outcomes.
Topics: Administration, Oral; Adult; Atorvastatin; Biphenyl Compounds; Cross-Over Studies; Drug Combinations; Healthy Volunteers; Humans; Male; Middle Aged; Pyrimidines; Tetrazoles; Young Adult
PubMed: 30087555
DOI: 10.2147/DDDT.S165171 -
Arquivos Brasileiros de Cardiologia Oct 2021
Topics: Anti-Inflammatory Agents; Anticholesteremic Agents; Atorvastatin; Humans; Metabolic Syndrome
PubMed: 34709301
DOI: 10.36660/abc.20210720 -
American Journal of Physiology.... Mar 2023The regulation of cholesterol metabolism in fish is still unclear. Statins play important roles in promoting cholesterol metabolism development in mammals. However,...
The regulation of cholesterol metabolism in fish is still unclear. Statins play important roles in promoting cholesterol metabolism development in mammals. However, studies on the role of statins in cholesterol metabolism in fish are currently limited. The present study evaluated the effects of statins on cholesterol metabolism in fish. Nile tilapia () were fed on control diets supplemented with three atorvastatin levels (0, 12, and 24 mg/kg diet, ATV0, ATV12, and ATV24, respectively) for 4 wk. Intriguingly, the results showed that both atorvastatin treatments increased hepatic cholesterol and triglyceride contents mainly through inhibiting bile acid synthesis and efflux, and compensatorily enhancing cholesterol synthesis in fish liver ( < 0.05). Moreover, atorvastatin treatment significantly inhibited hepatic very-low-density lipoprotein (VLDL) assembly and thus decreased serum VLDL content ( < 0.05). However, fish treated with atorvastatin significantly reduced cholesterol and triglycerides contents in adipose tissue ( < 0.05). Further molecular analysis showed that atorvastatin treatment promoted cholesterol synthesis and lipogenesis pathways, but inhibited lipid catabolism and low-density lipoprotein (LDL) uptake in the adipose tissue of fish ( < 0.05). In general, atorvastatin induced the remodeling of lipid distribution between liver and adipose tissues through blocking VLDL efflux from the liver to adipose tissue of fish. Our results provide a novel regulatory pattern of cholesterol metabolism response caused by atorvastatin in fish, which is distinct from mammals: cholesterol inhibition by atorvastatin activates hepatic cholesterol synthesis and inhibits its efflux to maintain cholesterol homeostasis, consequently reduces cholesterol storage in fish adipose tissue.
Topics: Animals; Atorvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoproteins; Cholesterol; Liver; Triglycerides; Lipoproteins, VLDL; Adipose Tissue; Lipid Metabolism; Mammals
PubMed: 36572553
DOI: 10.1152/ajpregu.00222.2022 -
Pharmacology 2023Autoimmune thyroiditis seems to be associated with increased cardiometabolic risk. Statins, the mainstay of cardiovascular risk reduction and prevention, were found to...
INTRODUCTION
Autoimmune thyroiditis seems to be associated with increased cardiometabolic risk. Statins, the mainstay of cardiovascular risk reduction and prevention, were found to reduce thyroid antibody titers. The aim of this study was to investigate plasma markers of cardiometabolic risk in statin-treated women with thyroid autoimmunity.
METHODS
We compared two matched groups of euthyroid women with hypercholesterolemia receiving atorvastatin treatment: subjects with autoimmune (Hashimoto's) thyroiditis (group A, n = 29) and subjects without thyroid pathology (group B, n = 29). Plasma lipids, glucose homeostasis markers, as well as circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D were measured before atorvastatin treatment and 6 months later.
RESULTS
At entry, both groups differed in antibody titers, insulin sensitivity, and plasma levels of uric acid, hsCRP, fibrinogen, homocysteine, and 25-hydroxyvitamin D. Atorvastatin-induced reduction in hsCRP and homocysteine, but not in total cholesterol and LDL-cholesterol, was more pronounced in group B than in group A. Only in group B, the drug decreased uric acid and fibrinogen and increased 25-hydroxyvitamin D. In group A, atorvastatin reduced insulin responsiveness.
CONCLUSION
The obtained results indicate that euthyroid women with Hashimoto's thyroiditis may benefit to a lesser degree from atorvastatin treatment than other populations of women with hypercholesterolemia.
Topics: Humans; Female; Atorvastatin; Hypercholesterolemia; Thyroiditis, Autoimmune; C-Reactive Protein; Cardiometabolic Risk Factors; Uric Acid; Risk Factors; Hashimoto Disease; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol; Fibrinogen; Cardiovascular Diseases
PubMed: 36878199
DOI: 10.1159/000529242