Optimal Low-Density Lipoprotein Cholesterol Lowering—Morning Versus Evening Statin Administration

Plakogiannis, Roda; Cohen, Henry

doi:10.1345/aph.1g659

Cited by 49 publications

(38 citation statements)

References 18 publications

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“…129 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase, the target of the statin family of inhibitors, oscillates in its expression, 130 whereas evening administration of these drugs achieves an optimal reduction in low-density lipoprotein (LDL). 131 There is circadian variation in the thrombolytic efficacy of tPA, which is most effective when administered between noon and midnight. 132 Thus, the timing of drug administration can be altered to improve therapeutic efficacy.…”

Section: Chronobiological Implications For Cardiovascular Therapymentioning

confidence: 99%

Peripheral Circadian Clocks in the Vasculature

Reilly

Westgate

FitzGerald

2007

ATVB

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Abstract-Living organisms have adapted to the daily rotation of the earth and regular changes in the light environment.Life forms anticipate environmental transitions, adapt their own physiology, and perform activities at behaviorally advantageous times during the day. This is achieved by means of endogenous circadian clocks that can be synchronized to the daily changes in external cues, most notably light and temperature. For many years it was thought that neurons of the suprachiasmatic nucleus (SCN) uniquely controlled circadian rhythmicity of peripheral tissues via neural and humoral signals. The cloning and characterization of mammalian clock genes revealed that they are expressed in a circadian manner throughout the body. It is now accepted that peripheral cells, including those of the cardiovascular system, contain a circadian clock similar to that in the SCN. Many aspects of cardiovascular physiology are subject to diurnal variation, and serious adverse cardiovascular events including myocardial infarction, sudden cardiac death, and stroke occur with a frequency conditioned by time of day. This has raised the possibility that biological responses under the control of the molecular clock might interact with environmental cues to influence the phenotype of human cardiovascular disease. (Arterioscler Thromb Vasc Biol. 2007;27:1694-1705.)ircadian rhythms are daily cycles of physiology and behavior that are driven by an endogenous oscillator with a period of approximately (circa-) one day (dies). 1 The most obvious circadian rhythm in humans is the cycle of sleep and wakefulness. 2 These cycles are not simply consequences of light perception, but are generated by endogenous circadian clocks that can adapt the physiology of an organism to its needs in an anticipatory manner. Their expression continues (free-runs) when subjects are isolated from the light cycle, with the oscillator defining predicted day and night, organizing our behavior and physiology appropriately to adapt to the contrasting demands encountered throughout the 24-hour period.Cardiovascular or hemodynamic parameters such as heart rate, blood pressure, endothelial function, and fibrinolytic activity exhibit variations consistent with circadian rhythm. Additionally, several types of acute pathological cardiac events exhibit diurnal patterns. The incidence of acute myocardial infarction, myocardial ischemia, cardiac arrest, ventricular tachycardia, post myocardial infarction, and sudden death in heart failure all vary according to the time of day. 3,4 Social and commercial pressures such as shift work, which oppose the temporal circadian order, may be underlying factors contributing to the incidence of chronic illnesses such as cardiovascular disease and cancer. 5,6 Understanding this molecular clock and its mechanisms may ultimately allow treatment of conditions where either the severity of the illness or therapeutic efficacy exhibit circadian rhythmicity. Molecular Basis of Circadian ClocksCircadian rhythms are regulated by three components: (1)...

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Section: Chronobiological Implications For Cardiovascular Therapymentioning

confidence: 99%

Peripheral Circadian Clocks in the Vasculature

Reilly

Westgate

FitzGerald

2007

ATVB

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“…However, robust trials are necessary to determine the best administration time to achieve optimal LDL-C lowering for rosuvastatin. 7) PK/PD modeling and simulation provide information on the relationship of the dosage regimen and the response to rosuvastatin. However, there are as yet no reports on a PK/PD model of rosuvastatin.…”

mentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Rosuvastatin Using an Extension of the Indirect Response Model by Incorporating a Circadian Rhythm

Aoyama

Omori

Watabe

et al. 2010

Biological & Pharmaceutical Bulletin

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In 2004, the United States Food and Drug Administration issued a "critical path" document for characterizing modelbased drug development as the development and application of pharmacostatistical models of drug efficacy and safety from preclinical and clinical data to improve drug development knowledge management and decision making.1,2) Pharmacokinetic/pharmacodynamic (PK/PD) modeling and simulation also enable the prediction of the effects of a medicine in various situations in clinical practice. The effective dosage regimen for acetaminophen in chronic pain patients was suggested by PK/PD modeling and simulation.3) The development of a safe, effective dosage regimen for sotalol was based on population PK/PD modeling and simulation.4) The PK/PD analysis of sotalol suggested a dosage regimen based on age and body weight. Thus PK/PD modeling and simulation provide a useful tool that is applicable in clinical practice.Rosuvastatin is a highly effective inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase. HMG-CoA reductase converts HMG-CoA to mevalonic acid (MVA). The inhibition of HMG-CoA reductase, which catalyzes the rate-limiting step of cholesterol biosynthesis in the liver, causes a decrease in the concentration of low-density lipoprotein cholesterol (LDL-C). The reduction in intracellular cholesterol concentration induces a subsequent upregulation of LDL-C receptors on the surface of hepatocytes, which results in an enhanced extraction of LDL-C from the blood and a decreased concentration of circulating LDL-C. MVA that is produced by the action of HMG-CoA reductase on HMG-CoA is the precursor of cholesterol. Plasma MVA concentration has been shown to be a good index of the in vivo rate of cholesterol synthesis.5) Despite the importance of HMG-CoA reductase inhibitors in the management of dyslipidemia, the relationship between drug exposure and the extent of HMG-CoA inhibition has not been elucidated. In general, peak cholesterol biosynthesis occurs at night, 6) suggesting that the hypocholesterolemic effects of HMG-CoA reductase inhibitors are stronger after evening administration than after morning administration. However, robust trials are necessary to determine the best administration time to achieve optimal LDL-C lowering for rosuvastatin. 7) PK/PD modeling and simulation provide information on the relationship of the dosage regimen and the response to rosuvastatin. However, there are as yet no reports on a PK/PD model of rosuvastatin.The aims of this study were to define the PK/PD model of rosuvastatin and to predict the response to rosuvastatin using simulated plasma MVA concentration in various dosage regimens such as poor compliance, and morning and evening dosage of rosuvastatin. Moreover, to clarify the PK parameter affecting the response to rosuvastatin, useful information was provided in clinical practice. MATERIALS AND METHODS Data SourceThe plasma rosuvastatin and MVA concentrations reported by Martin et al. 8) were used as the source of PK/PD modeling data. Graphs of concentration-tim...

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“…Nasuprot tomu, statine s dužim poluživotom (atorvastatin 14 sati, rosuvastatin 19 sati) može se propisivati u bilo koje doba dana 14 .…”

Section: Mehanizam Djelovanjaunclassified

“…On the other hand, statins with a longer half-life (atorvastatin 14 hours, rosuvastatin 19 hours) can be prescribed for any time of day 14 .…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Statins in the Prevention of Cardiovascular Diseases: Facts and Prejudices.

Lakušić¹

2016

Cardiol Croat.

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SAŽETAK: Unatoč brojnim dokazima o neposrednoj učinkovitosti statina u snizivanju ukupnog i LDL kolesterola te dugoročnih učinaka u primarnoj i sekundarnoj prevenciji srčanožilnih bolesti, još uvijek se u svakodnevnoj praksi susrećemo s različitim predrasudama vezanima za neželjene učinke liječe-nja i eventualnu štetnost statina ne samo bolesnika nego i nekih liječnika. Osnovni mehanizam djelovanja statina inhibicija je enzima hidroksi-metil-glutaril koenzima A reduktaze (HMG CoA), enzima koji je ključan u sintezi kolesterola. Drugi potencijalni mehanizmi njihove učinkovitosti jesu stabilizacija aterosklerotskoga plaka, smanjenje endotelne disfunkcije, upalnih te protrombotskih intravaskularnih procesa. Nuspojave liječenja statinima većinom su blage s učestalošću na razini placeba i najčešće ne zahtijevaju prekid liječenja. Treba istaknuti da uvijek treba poticati bolesnike na aktivni, nesedentarni način života, odnosno redovitu tjelesnu aktivnost, zbog njezinih jasnih pozitivnih uči-naka u prevenciji te u liječenju dislipidemije i srčanožilnih bolesti. SUMMARY:In spite of ample evidence supporting the direct effectiveness of statins in the reduction of total and low-density lipoprotein (LDL) cholesterol and long-term effects in primary and secondary prevention of cardiovascular diseases, in everyday practice we are still faced with various prejudices against the undesired effects of treatment and the possible adverse effects of statins, not only among patients, but among some physicians as well. The basic mechanism of action of statins is inhibiting 3-hydroxymethyl-3-methylglutaryl coenzyme A reductase (HMG-CoA), a key enzyme in cholesterol synthesis. Their other potential mechanisms are stabilization of atherosclerotic plaque and reduction of endothelial dysfunction, as well as inflammatory and post-thrombotic intravascular processes. The side effects of treatment with statins are generally mild, with a frequency comparable to placebo, and usually do not require the termination of treatment. It is necessary to emphasize that patients must always be encouraged to adopt an active, non-sedentary lifestyle that includes regular physical activity, due to its clear positive effects in the prevention and treatment of dyslipidemia and cardiovascular diseases.KLJUČNE RIJEČI: statini, dislipidemija, kardiovaskularna prevencija.

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Optimal Low-Density Lipoprotein Cholesterol Lowering—Morning Versus Evening Statin Administration

Cited by 49 publications

References 18 publications

Peripheral Circadian Clocks in the Vasculature

Peripheral Circadian Clocks in the Vasculature

Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Rosuvastatin Using an Extension of the Indirect Response Model by Incorporating a Circadian Rhythm

Statins in the Prevention of Cardiovascular Diseases: Facts and Prejudices.

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