Effects of Acid and Lactone Forms of Eight HMG-CoA Reductase Inhibitors on CYP-Mediated Metabolism and MDR1-Mediated Transport

@article{Sakaeda2005EffectsOA,
  title={Effects of Acid and Lactone Forms of Eight HMG-CoA Reductase Inhibitors on CYP-Mediated Metabolism and MDR1-Mediated Transport},
  author={Toshiyuki Sakaeda and Hideki Fujino and Chiho Komoto and Mikio Kakumoto and Jiang-shu Jin and Koichi Iwaki and Kohshi Nishiguchi and Tsutomu Nakamura and Noboru Okamura and Katsuhiko Okumura},
  journal={Pharmaceutical Research},
  year={2005},
  volume={23},
  pages={506-512}
}
PurposeWith the growing clinical usage of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), the number of reports concerning serious drug–drug interaction has been increasing. Because recent studies have shown that conversion between acid and lactone forms occurs in the body, drug–drug interaction should be considered on both acid and lactone forms. Thus, we investigated the inhibitory effects of acid and lactone forms of eight statins, including one recently withdrawn… Expand
Effects of acid and lactone forms of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on the induction of MDR1 expression and function in LS180 cells.
  • D. Yamasaki, Tsutomu Nakamura, +7 authors T. Sakaeda
  • Biology, Medicine
  • European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
  • 2009
TLDR
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Effects of acid and lactone forms of statins on S-warfarin 7-hydroxylation catalyzed by human liver microsomes and recombinant CYP2C9 variants (CYP2C9.1 and CYP2C9.3).
TLDR
Lactone forms of statins other than fluvastatin showed more potent inhibition of CYP2C9-catalyzed S-warfarin 7-hydroxylation than the corresponding acid forms. Expand
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TLDR
Current knowledge on substrates, inhibitors, inducers, and pharmacogenetics of CYP2C8, as well as its role in clinically relevant drug interactions is reviewed. Expand
Role of P‐glycoprotein in Statin Drug Interactions
TLDR
Drug interaction studies involving statins and digoxin support a role for P‐gp, an efflux protein located in the gastrointestinal tract, placenta, kidneys, brain, and liver, and many additional drugs such as diltiazem, verapamil, itraconazoles, ketoconazole, and cyclosporine, interact with statin and are modulators of both CYP3A4 and P‐ gp. Expand
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TLDR
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TLDR
Tested compounds can be considered safe in the terms of possible drug-drug interaction caused by induction of drug-metabolizing cytochromes P450, Nevertheless, mycophenolate mofetil is of possible concern and its combination with drugs, environmental pollutants or food constituents, which activate AhR, may represent a significant toxicological risk. Expand
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TLDR
The effects of cyclosporine and gemfibrozil explain the increased plasma statin concentrations and, together with pharmacodynamic factors, the increased risk of myotoxicity when coadministered with statins. Expand
Statins in therapy: Cellular transport, side effects, drug-drug interactions and cytotoxicity -the unrecognized role of lactones
Abbreviations: drug-drug interactions (DDI), human serum albumin (HSA), area under the curve fold ratio (AUCR), free energy change (ΔG), electron affinity (EA), reactive oxygen species (ROS),Expand
Pharmacokinetic Comparison of the Potential Over-the-Counter Statins Simvastatin, Lovastatin, Fluvastatin and Pravastatin
TLDR
On the pharmacokinetic basis, fluvastatin and pravastatin can be better choices than simVastatin or lovastatin for an OTC statin, but their concomitant use needs medical supervision. Expand
ERSPECTIVES IN CLINICAL HARMACOLOGY rug interactions with lipid-lowering rugs : Mechanisms and clinical relevance
Lipid-lowering drugs, especially 3-hydroxy-3-methylglutaryl–coenzyme A inhibitors (statins), are widely used in the treatment and prevention of atherosclerotic disease. The benefits of statins areExpand
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TLDR
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TLDR
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TLDR
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TLDR
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The active forms of all marketed hydroxymethylglutaryl (HMG)-CoA reductase inhibitors share a common dihydroxy heptanoic or heptenoic acid side chain. In this study, we present evidence for theExpand
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TLDR
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TLDR
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TLDR
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