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Related Experiment Videos

Erythromycin coadministration increases plasma atorvastatin concentrations.

P H Siedlik1, S C Olson, B B Yang

  • 1Department of Pharmacokinetics, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.

Journal of Clinical Pharmacology
|May 11, 1999
PubMed
Summary

This study found that co-administering erythromycin with atorvastatin (a cholesterol-lowering drug) significantly increased atorvastatin levels in healthy volunteers. This drug interaction may affect statin therapy safety and efficacy.

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Area of Science:

  • Pharmacology
  • Drug Interactions
  • Clinical Pharmacology

Background:

  • Atorvastatin is a widely prescribed HMG-CoA reductase inhibitor for managing hypercholesterolemia.
  • Erythromycin is a common antibiotic that can interact with other medications.
  • Understanding drug interactions is crucial for patient safety and effective treatment.

Purpose of the Study:

  • To investigate the pharmacokinetic interaction between erythromycin and atorvastatin in healthy volunteers.
  • To determine the effect of erythromycin on atorvastatin Cmax, AUC(0-infinity), and terminal half-life.

Main Methods:

  • A pharmacokinetic study involving 12 healthy volunteers.
  • Subjects received atorvastatin 10 mg alone and with erythromycin (500 mg qid).
  • Atorvastatin and active metabolite concentrations were measured using an enzyme inhibition assay.

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Main Results:

  • Coadministration with erythromycin resulted in a 37.7% increase in atorvastatin Cmax.
  • Mean AUC(0-infinity) for atorvastatin increased by 32.5% when given with erythromycin.
  • The terminal half-life of atorvastatin remained similar in both treatment arms.

Conclusions:

  • Erythromycin significantly alters the pharmacokinetics of atorvastatin, increasing its exposure.
  • Potential mechanisms include inhibition of atorvastatin's first-pass metabolism and P-glycoprotein-mediated transport.
  • These findings highlight a clinically relevant drug interaction that may impact atorvastatin dosing and monitoring.