Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin

  title={Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin},
  author={Arthur Mazzu and Kenneth C. Lasseter and E. C. Shamblen and Vipin Agarwal and John T. Lettieri and Pavur Sundaresen},
  journal={Clinical Pharmacology \& Therapeutics},
3‐Hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (statins) are metabolized by distinct pathways that may alter the extent of drug‐drug interactions. Cerivastatin is metabolized by cytochrome P450 (CYP)3A4 and CYP2C8. Atorvastatin is metabolized solely by CYP3A4, and pravastatin metabolism is not well defined. Coadministration of higher doses of these statins with CYP3A4 inhibitors has the potential for eliciting adverse drug‐drug interactions. 

Effect of itraconazole on the pharmacokinetics of rosuvastatin

Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro *

Both atorVastatin and fluvastatin inhibit the CYP 3A4‐mediated metabolism of midazolam in vitro, using pooled human liver microsomes.

Role of P‐glycoprotein in Statin Drug Interactions

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.

ERSPECTIVES IN CLINICAL HARMACOLOGY rug interactions with lipid-lowering rugs : Mechanisms and clinical relevance

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.

Utilization of In Vitro Cytochrome P450 Inhibition Data for Projecting Clinical Drug–Drug Interactions

The current knowledge base and the complexities of CYP inhibition are summarized and a guide for embarking on prediction of clinical DDIs with particular emphasis on the drug discovery setting is provided.

Controversy surrounding the safety of cerivastatin

The noted myotoxicity and subsequent withdrawal of cerivastatin from the worldwide market in August 2001 has demonstrated that the safety of statins is not a class effect and insights into high-risk populations that are more prone to statin-induced myopathy are provided.

Comparative Analysis of Clinical and Non-Clinical Pharmacokinetic Interactions of Statins with Other Drugs

Due to several complicating factors such as plasma protein binding, first pass effect, lipophilicity/hydrophilicity, and inter-conversion between acid and lactone forms, further clinical pharmacokinetic interaction studies will be needed to predict the likelihood of drug interactions.

Relationship between Statins Adverse Events and Pharmacokinetic Variables

There are no doubts that statins together with steroids, antibiotics and diuretics are among the most important drugs of the last two centuries. Despite the improvement of the life expectancy,



Effect of itraconazole on the pharmacokinetics of atorvastatin

Itraconazole drastically increases plasma concentrations of lovastatin and lovastatin acid

Erythromycin Coadministration Increases Plasma Atorvastatin Concentrations

The effect of erythromycin on the pharmacokinetics of atorvastatin, an inhibitor of HMG‐CoA reductase, was investigated in 12 healthy volunteers and it was found that mean terminal half‐life was similar following each atorVastatin dose.

Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole.

To the Editor: Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, widely prescribed to treat hypercholesterolemia, are clearly effective and are associated with reductions in ...

Atorvastatin: a hydroxymethylglutaryl-coenzyme A reductase inhibitor.

  • J. M. Malinowski
  • Biology
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
  • 1998
Atorvastatin effectively reduces blood lipids and may offer some advantages over other statins, but more studies are needed to clarify its optimal role in pharmacotherapy.

Effect of itraconazole on cerivastatin pharmacokinetics

Inhibition of the CYP3A4-mediated M-1 metabolic pathway leads to elevated serum concentrations of cervastatin, cerivastatin lactone and metabolite M-23, resulting in increased concentrations of active HMG-CoA reductase inhibitors.

Clinical efficacy and safety of cerivastatin: summary of pivotal phase IIb/III studies.

Preclinical and clinical pharmacology of cerivastatin.