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Molecular Mechanisms for Statin Pleiotropy and Possible Clinical Relevance in Cardiovascular Disease
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Brian Yu, Nikola Sladojevic, James K. Liao
Initial evidence for statin pleiotropy came from subgroup analyses of the West of Scotland Coronary Prevention Study (WOSCOP) and Cholesterol and Recurrent Events (CARE) clinical trials, showing individuals on statin treatment have significantly lower risks for CHD compared to age-matched placebo-controlled individuals, despite comparable serum cholesterol levels (Shepherd et al., 1995; Sacks et al., 1996). Furthermore, dividing the statin treatment group into quintiles of percentage LDL-C reduction revealed there was no apparent association between coronary event rate and percentage LDL-C reduction, suggesting there were perhaps other mechanisms by which statins exert cardioprotective effects. The more recent Justification for the Use of Statins in prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study showed the realized benefit of rosuvastatin was greater than the expected benefit of LDL-C reduction alone, perhaps due to reductions in the level of C-reactive protein (CRP), an important inflammatory marker (Fig. 10.3) (Ridker et al., 2008). Some smaller clinical trials have also found evidence for statin benefits beyond cholesterol lowering, primarily through beneficial effects on endothelial function and inflammation (Liu et al., 2009; Antoniades et al., 2011; Antoniades et al., 2010).
Enzyme Kinetics and Drugs as Enzyme Inhibitors
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Statins (atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) act as competitive HMG-CoA reductase inhibitors; HMG-CoA reductase is the first enzyme in the mevalonate pathway for synthesizing cholesterol in the liver that begins with the conversion of acetyl-CoA to mevalonate. They lower LDL-C by 18% to 55%, but are not as effective in treating familial hypercholesterolemia, an autosomal dominant disorder; this holds in particular for people with homozygous defects usually in either the LDL receptor or apolipoprotein B genes, which both are responsible for LDL clearance from the blood. Statins have been found to reduce cardiovascular disease; side/adverse effects of statins are muscle pain, increased risk of diabetes mellitus (statins and niacin are associated with increased risk of impaired glucose control and development of new-onset diabetes; Zafrir and Jain, 2014), abnormalities in liver enzyme, liver damage, cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction (Golomb et al., 2008; Thompson et al., 2016) myopathies and muscles inflammation (Abd and Jacobson, 2011). For a “Protocol for analyses of adverse event data from randomized controlled trials of statin therapy” see Reith et al. (2016). In contrast to earlier findings, e.g., those published by Gao et al. (2012), who reported that regular use of statins was associated with a modest reduction in PD risk, a new study performed by Liu et al. (2017) came to the conclusion that the use of statins in particular lipophilic ones, is associated with a significantly higher risk of developing symptoms of Parkinson’s disease.
Garlic oil loaded rosuvastatin solid self-nanoemulsifying drug delivery system to improve level of high-density lipoprotein for ameliorating hypertriglyceridemia
Published in Particulate Science and Technology, 2022
Adnan Burhan Qader, Shobhit Kumar, Kanchan Kohli, Ahmed Abbas Hussein
Rosuvastatin is an anti-hyperlipidemic drug. It is generally employed to treat hypercholesterolemia. Benign Alzheimer's disease, prostatic hyperplasia and osteoporosis were also treated with rosuvastatin (Ahsana et al. 2013; Salem et al. 2018). This drug is a BCS class II drug that displays low dissolution due to its crystalline nature and, thus, 20% reduced oral bioavailability. This is also metabolized widely in liver (Salem et al. 2018). Although of its poor water solubility, oral bioavailability of rosuvastatin is poor (Ahsana et al. 2013). There was a need to develop S-SNEDDS to resolve problems with rosuvastatin, which increases the oral bioavailability of rosuvastatin. Present study thus aimed at developing rosuvastatin S-SNEDDS using a spray drying technique using Aerosil 200 as a solid carrier for enhanced oral bioavailability. Objective of this study was to develop a solid self˗nanoemulsifying rosuvastatin drug delivery system (S-SNEDDS) for enhancement of its oral bioavailability and to produce synergistic action with garlic oil for better management of hypertriglyceridemia. To date no S-SNEDDS formulation was developed for synergistic action of garlic oil and rosuvastatin.
Reproductive outcomes in rat female offspring from male rats co-exposed to rosuvastatin and ascorbic acid during pre-puberty
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Gabriel Adan Araujo Leite, Thamiris Moreira Figueiredo, Tainá Louise Pacheco, Marina Trevizan Guerra, Janete Aparecida Anselmo-Franci, Wilma De Grava Kempinas
Rosuvastatin is the most recent statin available in the market used for lipid-lowering treatment and shows superior inhibitory effects on cholesterol biosynthesis in relation to the other statins (Holdgate, Ward, and McTaggart 2003; McTaggart 2003; Olsson, McTaggart, and Raza 2002). Statins are recommended to be administered as a daily dose during the evening, although rosuvastatin may be used any time of the day due to its long half-life (Martin, Mitchell, and Schneck 2002). In addition, the long half-life of rosuvastatin enables administration on alternate days; however, this regimen is not as effective as daily dosing of rosuvastatin (Dulay et al. 2009).