Fixed Combination of Amlodipine/Atorvastatin

Ivanović, Branislava; Tadić, Marijana

doi:10.1177/1074248413492907

Cited by 6 publications

(3 citation statements)

References 28 publications

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“…The authors calculated the theoretical risk reductions of ischemic heart disease and stroke using the polypill [84]. The main advantages of the polypill are increased effectiveness, enhanced adherence, and lower cost [67]. However, the use of the polypill in primary prevention is controversial.…”

Section: The Role Of the Polypill In Blood Pressure And Cholesterol Lmentioning

confidence: 99%

Hypercholesterolemia and Hypertension: Two Sides of the Same Coin

Ivanović

Tadić

2015

Am J Cardiovasc Drugs

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The aim of this review article is to summarize the current knowledge about mechanisms that connect blood pressure regulation and hypercholesterolemia, the mutual interaction between hypertension and hypercholesterolemia, and their influence on atherosclerosis development. Our research shows that at least one-third of the population of Western Europe has hypertension and hypercholesterolemia. Several biohumoral mechanisms could explain the relationship between hypertension and hypercholesterolemia and the association between these risk factors and accelerated atherosclerosis. The most investigated mechanisms are the renin-angiotensin-aldosterone system, oxidative stress, endothelial dysfunction, and increased production of endothelin-1. Arterial hypertension is frequently observed in combination with hypercholesterolemia, and this is related to accelerated atherosclerosis. Understanding the mechanisms behind this relationship could help explain the benefits of therapy that simultaneously reduce blood pressure and cholesterol levels.

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Section: The Role Of the Polypill In Blood Pressure And Cholesterol Lmentioning

confidence: 99%

Hypercholesterolemia and Hypertension: Two Sides of the Same Coin

Ivanović

Tadić

2015

Am J Cardiovasc Drugs

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“…CVD is multifactorial, with risk factors such as hypertension, dyslipidemia, diabetes mellitus, smoking, and obesity frequently coexisting 2. One of the most common risk factor combinations is dyslipidemia (elevated levels of low-density lipoprotein [LDL] and triglyceride and low levels of high-density lipoprotein [HDL]) and hypertension 3.…”

Section: Introductionmentioning

confidence: 99%

Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability

Dennison¹,

Smith²,

Badhan³

et al. 2017

DDDT

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Cardiovascular disease (CVD) is the leading cause of death among men and women worldwide. In CVD, hypertension and dyslipidemia commonly coexist and are managed through coadministration of amlodipine and atorvastatin, respectively. The case for fixed-dose combination (FDC) oral dosage forms and orally disintegrating tablet (ODT) technology to enhance outcomes and compliance is strong. This work follows the development and characterization of single and FDC ODTs containing amlodipine and atorvastatin, followed by bioequivalence comparison between these single and FDC formulations, using in vitro dissolution and Caco-2 apparent permeability (Papp) and in silico physiologically based pharmacokinetic modeling approaches. ODTs containing amlodipine (5 mg) and atorvastatin (10 mg) either alone or in combination rapidly disintegrated (<30 s) while displaying a radial crushing strength in excess of 100 N and friability ≤1%. In vitro dissolution test was performed in fasted and fed-state simulated intestinal fluid (FeSSIF) and analyzed using high-performance liquid chromatography. Dissolution profiles for single and FDC ODTs were compared using US FDA recommended difference (f1) and similarity (f2) factor testing for bioequivalence. In all cases, there was no difference in active pharmaceutical ingredient dissolution between single or FDC ODTs, with the exception of amlodipine in FeSSIF. Pharmacokinetic clinical trial simulations were conducted using Simcyp (Version 14), incorporating Papp and dissolution data. Simulated clinical trials in healthy volunteers showed no difference in bioavailability based on pharmacokinetic parameters between single and combination doses with either active pharmaceutical ingredient. An increase in Cmax and AUC for atorvastatin in fed subjects was attributed to extended transit along the gut lumen and reduced atorvastatin metabolism due to lower CYP3A4 expression at more distal small intestine absorption sites. The results demonstrated bioequivalence of an FDC ODT for amlodipine and atorvastatin, while highlighting several limitations of f1 and f2 bioequivalence testing and strengths of mechanistic pharmacokinetic modeling for oral drug absorption.

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“…Furthermore, dyslipidemia is one of the main alterations characterizing the metabolic syndrome . Oxidation of LDL promotes inflammatory response, which includes impaired vasomotor function, platelet, and leukocyte adhesion to endothelial cells and increased free radical production, leading to plaque vulnerability . Dyslipidemias are not adequately diagnosed and treated, thus, they are still poorly controlled, mainly because the origin of atherosclerosis is still not completely understood .…”

Section: Introductionmentioning

confidence: 99%

Thiomorpholine Derivatives with Hypolipidemic and Antioxidant Activity

Tooulia

Theodosis-Nobelos

Rekka

2015

Archiv der Pharmazie

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A number of thiomorpholine derivatives that are structurally similar to some substituted morpholines possessing antioxidant and hypocholesterolemic activity were synthesized. The new compounds incorporate an antioxidant moiety as the thiomorpholine N-substituent. The derivatives were found to inhibit the ferrous/ascorbate-induced lipid peroxidation of microsomal membrane lipids, with IC50 values as low as 7.5 µΜ. In addition, these compounds demonstrate hypocholesterolemic and hypolipidemic action. The most active compound (5) decreases the triglyceride, total cholesterol, and low-density lipoprotein levels in the plasma of Triton WR-1339-induced hyperlipidemic rats, by 80, 78, and 76%, respectively, at 56 mmol/kg (i.p.). They may also act as squalene synthase inhibitors. The above results indicate that the new molecules may be useful as leads for the design of novel compounds as potentially antiatherogenic factors.

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Fixed Combination of Amlodipine/Atorvastatin

Cited by 6 publications

References 28 publications

Hypercholesterolemia and Hypertension: Two Sides of the Same Coin

Hypercholesterolemia and Hypertension: Two Sides of the Same Coin

Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability

Thiomorpholine Derivatives with Hypolipidemic and Antioxidant Activity

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