Drug interactions with lipid‐lowering drugs: Mechanisms and clinical relevance

@article{Neuvonen2006DrugIW,
  title={Drug interactions with lipid‐lowering drugs: Mechanisms and clinical relevance},
  author={Pertti J. Neuvonen and Mikko Niemi and Janne T. Backman},
  journal={Clinical Pharmacology \& Therapeutics},
  year={2006},
  volume={80}
}

Drug–drug interactions that interfere with statin metabolism

The pharmacokinetic aspects of the drug–drug interaction with statins and genetic polymorphisms in CYPs, which are involved in the metabolism of statins, are discussed and the importance of establishing a system utilizing electronic medical information practically to avoid adverse drug reactions is highlighted.

Effects of Statins on the Pharmacokinetics of Midazolam in Healthy Volunteers

The data suggest that statins, at least at low doses used in the present study, do not affect CYP3A4 and can be used safely without influencing CAP3A 4 enzyme activity.

Drug–Drug Interactions Between HMG-CoA Reductase Inhibitors (Statins) and Antiviral Protease Inhibitors

Simvastatin and lovastatin have the highest potency for drug–drug interaction with potent CYP3A inhibitors such as ritonavir- or cobicistat-boosted HIV-PI or the hepatitis C virus, telaprevir or boceprevir, and therefore their coadministration is contraindicated.

Pharmacokinetic Comparison of the Potential Over-the-Counter Statins Simvastatin, Lovastatin, Fluvastatin and Pravastatin

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.

An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins

The establishment of biomarkers based on novel mechanisms, such as the leakage of microRNAs into the peripheral blood associated with the muscle toxicity, is important for the early detection of statin side effects.

Risks of Adverse Events Following Coprescription of Statins and Calcium Channel Blockers

Patients who received CYP3A4-metabolized statins had significantly higher risk of acute kidney injury, hyperkalemia, acute myocardial infarction, and acute ischemic stroke than those who received non-CYP3A 4-metabolic statins.

Drug–drug interaction with statins

The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently.

Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions

Current knowledge on substrates, inhibitors, inducers, and pharmacogenetics of CYP2C8, as well as its role in clinically relevant drug interactions is reviewed.

Comparative Hepatic and Intestinal Metabolism and Pharmacodynamics of Statins

Compared with in vitro drug transporter and clinical data, the findings are applicable for use in comparative systems pharmacology modelling to predict the pharmacokinetics and pharmacological effects of statins at different dosages.
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References

SHOWING 1-10 OF 173 REFERENCES

Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update

  • M. Schachter
  • Biology, Chemistry
    Fundamental & clinical pharmacology
  • 2005
Clinical studies have demonstrated rosuvastatin to be the most effective for reducing low‐density lipoprotein cholesterol, followed by atorvastsatin, simvastasin and pravastatin, and the bioavailability of the statins differs greatly, from 5% for lovastatin and simvASTatin to 60% or greater for cerivastatinand pitavastatin.

HMG-CoA Reductase Inhibitors (Statins) Characterized as Direct Inhibitors of P-Glycoprotein

This study shows directly, as well as quantifies, the inhibition of P-gp-mediated transport of a fluorescent marker substrate, which indicates that the clinical interactions of statins with other drugs may be due, in part or all, to inhibition ofP-gp transport.

Clinical Pharmacokinetics of Fluvastatin

Fluvastatin is relatively hydrophilic, compared with the semisynthetic HMG-CoA reductase inhibitors, and, therefore, it is extensively absorbed from the gastrointestinal tract, and does not appear to have a significant effect on other CYP isoenzymes or P-glycoprotein-mediated transport in vivo.

Pharmacokinetic-Pharmacodynamic Drug Interactions with HMG-CoA Reductase Inhibitors

Rhabdomyolysis has occurred following the coadministration of cyclosporin, a potent CYP3A4 and P-glycoprotein inhibitor, and lovastatin, and the patient should be monitored for signs and symptoms of myopathy and the statin should be discontinued if necessary.

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

The difference between the acid and lactone forms in terms of drug interaction was showed, and a significant correlation was found between the lipophilicity and inhibitory effects on CYP2C8-mediated paclitaxel 6α-hydroxylation.

Interactions between cyclosporin and lipid-lowering drugs: implications for organ transplant recipients.

There is no information on possible interaction effects of cyclosporin on the pharmacokinetics of lipid-lowering drugs other than statins, but it is not likely that any clinical relevant interference exists with fish oil, orlistat, probucol or bile acid sequestrants.

In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors

Fluvastatin selectively inhibits a major drug metabolising enzyme (CYP2C9), the (+)-isomer (pharmacologically more active) showing 4–5 fold higher affinity.

Metabolic properties of the acid and lactone forms of HMG-CoA reductase inhibitors

It is demonstrated that CYP-mediated metabolism of lactones is also a common metabolic pathway for statins and that the CYP3A4- mediated metabolism of the lactone forms clearly will need to be taken into account in assessing mechanistic aspects of drug–drug interaction involving statins.
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