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Cited by 796Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismCancer, Lipids, and Metabolism

The DOI matches its Crossref record; 187 of the 187 references it cites were found in a registry or an index.

New insights into the pharmacodynamic and pharmacokinetic properties of statins

Corsini, Alberto, Bellosta, Stefano, Baetta, Roberta, Fumagalli, Remo, Paoletti, Rodolfo, Bernini, Franco·1999·Pharmacology & Therapeutics
DOI 10.1016/s0163-7258(99)00045-5
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Abstract

The beneficial effects of statins are assumed to result from their ability to reduce cholesterol biosynthesis. However, because mevalonic acid is the precursor not only of cholesterol, but also of many nonsteroidal isoprenoid compounds, inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase may result in pleiotropic effects. It has been shown that several statins decrease smooth muscle cell migration and proliferation and that sera from fluvastatin-treated patients interfere with its proliferation. Cholesterol accumulation in macrophages can be inhibited by different statins, while both fluvastatin and simvastatin inhibit secretion of metalloproteinases by human monocyte-derived macrophages. The antiatherosclerotic effects of statins may be achieved by modifying hypercholesterolemia and the arterial wall environment as well. Although statins rarely have severe adverse effects, interactions with other drugs deserve attention. Simvastatin, lovastatin, cerivastatin, and atorvastatin are biotransformed in the liver primarily by cytochrome P450-3A4, and are susceptible to drug interactions when co-administered with potential inhibitors of this enzyme. Indeed, pharmacokinetic interactions (e.g., increased bioavailability), myositis, and rhabdomyolysis have been reported following concurrent use of simvastatin or lovastatin and cyclosporine A, mibefradil, or nefazodone. In contrast, fluvastatin (mainly metabolized by cytochrome P450-2C9) and pravastatin (eliminated by other metabolic routes) are less subject to this interaction. Nevertheless, a 5- to 23-fold increase in pravastatin bioavailability has been reported in the presence of cyclosporine A. In summary, statins may have direct effects on the arterial wall, which may contribute to their antiatherosclerotic actions. Furthermore, some statins may have lower adverse drug interaction potential than others, which is an important determinant of safety during long-term therapy.

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Citations

Cites

Research works printed but not linked: 8

  1. Fischer, 1999, The HMG-CoA reductase inhibitor fluvastatin, Drug Metab Dispos, 27, 410
  2. Henwood, 1995, Lovastatin. A preliminary review of its pharmacodynamic properties and therapeutic use in hyperlipidaemia, Drugs, 31, 9
  3. Hoffman, 1992, The interaction of lovastatin and warfarin, Conn Med, 56, 107
  4. Mai, 1997, Clinical pharmacokinetics of a new HMG-CoA reductase inhibitor in renal transplant patients treated with cyclosporin A (CSA), Eur J Clin Pharmacol, 52, A137
  5. Raiteri, 1997, Pharmacological control of the mevalonate pathway, J Pharmacol Exp Ther, 281, 1144
  6. 1994, Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease, Lancet, 344, 1383
  7. Smith, 1991, HMG-CoA reductase inhibitor-induced myopathy in the rat, J Pharmacol Exp Ther, 257, 1225
  8. Soma, 1995, In vitro and in vivo enhanced anti-tumor activity of carmustine (BCNU) by simvastatin, a hypocholesterolemic drug, Cancer Res, 55, 597

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Metadata

Authors
Corsini, A., Bellosta, S., Baetta, R., Fumagalli, R., Paoletti, R., & Bernini, F.
Affiliations
  • University of Milan (IT)
  • University of Parma (IT)
Corresponding author
Corsini, Alberto
ORCID
Venue
Pharmacology & Therapeutics
Publisher
Elsevier BV
Published
1999-12
Volume
84
Issue
3
Pages
413-428
ISSN
0163-7258 (ISSN-L)
DOI
10.1016/s0163-7258(99)00045-5
OpenAlex
W2045063002
Cited by
796
References
186
Citations by year
2026: 5 · 2025: 6 · 2024: 27 · 2023: 19 · 2022: 17 · 2021: 25 · 2020: 17 · 2019: 14 · 2018: 21 · 2017: 30 · 2016: 30 · 2015: 27 · 2014: 35 · 2013: 31 · 2012: 38
FWCI
5.97
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Pharmacology & Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
statins, pharmacokinetics, pharmacodynamics, HMG-CoA reductase inhibition, mevalonate, pleiotropy, smooth muscle cell proliferation, macrophage cholesterol accumulation, atherosclerosis, drug interactions, CYP3A4, cyclosporine, rhabdomyolysis, myositis, pravastatin, fluvastatin, simvastatin, lovastatin, atorvastatin, cerivastatin
MeSH terms
Atorvastatin, Fluvastatin, Animals, Anticholesteremic Agents, Cell Division, Cytochrome P-450 Enzyme System, Drug Interactions, Fatty Acids, Monounsaturated, Heptanoic Acids, Humans, Indoles, Mevalonic Acid, Pyridines, Pyrroles, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin

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