Fluvastatin for lowering lipids

Adams, Stephen P.; Sekhon, Sarpreet S; Tsang, Michael; Wright, James M

doi:10.1002/14651858.cd012282.pub2

Cited by 49 publications

(17 citation statements)

References 216 publications

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“…Hence, montelukast can be tried for drug repurposing with detailed studies. Fluvastatin is a hypolipidemic agent belongs to the class statins 33 . Because of their pleiotropic role, statins can be explored further to repurpose to COVID-19.…”

Section: Resultsmentioning

confidence: 99%

Targeting SARS-CoV-2 RNA-dependent RNA polymerase: An in silico drug repurposing for COVID-19

et al. 2020

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Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), took more lives than combined epidemics of SARS, MERS, H1N1, and Ebola. Currently, the prevention and control of spread are the goals in COVID-19 management as there are no specific drugs to cure or vaccines available for prevention. Hence, the drug repurposing was explored by many research groups, and many target proteins have been examined. The major protease (Mpro), and RNA-dependent RNA polymerase (RdRp) are two target proteins in SARS-CoV-2 that have been validated and extensively studied for drug development in COVID-19. The RdRp shares a high degree of homology between those of two previously known coronaviruses, SARS-CoV and MERS-CoV. Methods: In this study, the FDA approved library of drugs were docked against the active site of RdRp using Schrodinger's computer-aided drug discovery tools for in silico drug-repurposing. Results: We have shortlisted 14 drugs from the Standard Precision docking and interaction-wise study of drug-binding with the active site on the enzyme. These drugs are antibiotics, NSAIDs, hypolipidemic, coagulant, thrombolytic, and anti-allergics. In molecular dynamics simulations, pitavastatin, ridogrel and rosoxacin displayed superior binding with the active site through ARG555 and divalent magnesium. Conclusion: Pitavastatin, ridogrel and rosoxacin can be further optimized in preclinical and clinical studies to determine their possible role in COVID-19 treatment.

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Section: Resultsmentioning

confidence: 99%

Targeting SARS-CoV-2 RNA-dependent RNA polymerase: An in silico drug repurposing for COVID-19

et al. 2020

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“…The site of action of statins is within the hepatocytes, and fluvastatin efficacy is therefore related to the hepatocyte exposure to 3R,5S‐fluvastatin . The maximum fluvastatin dose (80 mg/day) reduces Low‐density lipoprotein cholesterol on average by 33%, which is less than that seen with the maximum doses of rosuvastatin and atorvastatin. As the CYP2C9*3 and *2 variants impair the hepatic metabolism of fluvastatin, they should increase the hepatocyte concentration of 3R,5S‐fluvastatin to at least the same extent as its plasma concentration and therefore enhance its cholesterol‐lowering efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…As the CYP2C9*3 and *2 variants impair the hepatic metabolism of fluvastatin, they should increase the hepatocyte concentration of 3R,5S‐fluvastatin to at least the same extent as its plasma concentration and therefore enhance its cholesterol‐lowering efficacy. Low‐density lipoprotein cholesterol decreases by 6% for every twofold increase in fluvastatin dose . Therefore, individuals with, e.g., the CYP2C9*2/*3 genotype, associated with twofold increased 3R,5S‐fluvastatin AUC ( Figure ), should show at least 6% greater low‐density lipoprotein cholesterol‐lowering efficacy of fluvastatin than individuals with the *1/*1 genotype.…”

Section: Discussionmentioning

confidence: 99%

Enantiospecific Pharmacogenomics of Fluvastatin

Hirvensalo

Tornio

Neuvonen

et al. 2019

Clin Pharma and Therapeutics

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The aim of this study was to investigate how variability in multiple genes related to pharmacokinetics affects fluvastatin exposure. We determined fluvastatin enantiomer pharmacokinetics and sequenced 379 pharmacokinetic genes in 200 healthy volunteers. CYP2C9*3 associated with significantly increased area under the plasma concentration‐time curve (AUC) of both 3R,5S‐fluvastatin and 3S,5R‐fluvastatin (by 67% and 94% per variant allele copy, P = 3.77 × 10−9 and P = 3.19 × 10−12). In contrast, SLCO1B1 c.521T>C associated with increased AUC of active 3R,5S‐fluvastatin only (by 34% per variant allele copy; P = 8.15 × 10−8). A candidate gene analysis suggested that CYP2C9*2 also affects the AUC of both fluvastatin enantiomers and that SLCO2B1 single‐nucleotide variations may affect the AUC of 3S,5R‐fluvastatin. Thus, SLCO transporters have enantiospecific effects on fluvastatin pharmacokinetics in humans. Genotyping of both CYP2C9 and SLCO1B1 may be useful in predicting fluvastatin efficacy and myotoxicity.

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“…Also, it seems unlikely that subjective expectations or a placebo effect could occur for the non‐acute biological outcomes of muscle fiber type proportions and muscle fiber CSA. This handling is equal to other placebo‐unaffected biological outcomes published by the Cochrane collaboration such as for blood cholesterol 40‐42 …”

Section: Methodsmentioning

confidence: 99%

Human skeletal muscle fiber type percentage and area after reduced muscle use: A systematic review and meta‐analysis

Vikne¹,

Strøm

Pripp

et al. 2020

Scandinavian Med Sci Sports

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The main objective of this systematic review was to examine the effect of reduced muscle activity on the relative number of type 1 muscle fibers (%) in the human vastus lateralis muscle. Other objectives were changes in type 2A and 2X percentages and muscle fiber cross‐sectional area. We conducted systematic literature searches in eight databases and included studies assessing type 1 fiber percentage visualized by ATPase or immunohistochemical staining before and after a period (≥14 days) of reduced muscle activity. The reduced muscle activity models were detraining, leg unloading, and bed rest. Forty‐two studies comprising 451 participants were included. Effect sizes were calculated as the mean difference between baseline and follow‐up and Generic Inverse Variance tests with random‐effects models were used for the weighted summary effect size. Overall, the mean type 1 muscle fiber percentage was significantly reduced after interventions (−1.94%‐points, 95% CI [−3.37, −0.51], P = .008), with no significant differences between intervention models (P = .86). Meta‐regression showed no effect of study duration on type 1 fiber percentage (P = .98). Conversely, the overall type 2X fiber percentage increased after reduced muscle activity (P < .001). The CSA of the muscle fiber types decreased after the study period (all P‐values < 0.001) with greater reductions in type 2 than type 1 fibers (P < .001). The result of this meta‐analysis display that the type 1 muscle fiber percentage decrease as a result of reduced muscle activity, although the effect size is relatively small.

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Fluvastatin for lowering lipids

Cited by 49 publications

References 216 publications

Targeting SARS-CoV-2 RNA-dependent RNA polymerase: An in silico drug repurposing for COVID-19

Targeting SARS-CoV-2 RNA-dependent RNA polymerase: An in silico drug repurposing for COVID-19

Enantiospecific Pharmacogenomics of Fluvastatin

Human skeletal muscle fiber type percentage and area after reduced muscle use: A systematic review and meta‐analysis

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