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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
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.
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.
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.