The effect of erythromycin on the pharmacokinetics of rosuvastatin

Eur J Clin Pharmacol. 2003 May;59(1):51-6. doi: 10.1007/s00228-003-0573-7. Epub 2003 Apr 1.

Abstract

Rationale objective: To examine in vivo the effect of erythromycin on the pharmacokinetics of rosuvastatin [an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase]. Erythromycin is a potent inhibitor of CYP3A4 that markedly increases circulating levels of some other HMG-CoA reductase inhibitors.

Methods: In this randomised, double-blind, two-way cross-over, placebo-controlled trial 14 healthy volunteers were given 500 mg erythromycin or placebo four times daily for 7 days. A single dose of 80 mg rosuvastatin was co-administered on day 4 of dosing. Plasma concentrations of rosuvastatin and active and total HMG-CoA reductase inhibitors were measured up to 96 h after dosing.

Results: Eleven volunteers had data available from both dosing periods. There was no increase in rosuvastatin plasma exposure following co-administration with erythromycin compared to placebo. In fact, following co-administration with erythromycin, rosuvastatin geometric least square mean AUC((0-t)) and C(max) were 20% and 31%, respectively, lower than with placebo. Individual treatment ratios for AUC((0-t)) ranged from 0.48 to 1.17, and for C(max) ranged from 0.33 to 2.19. Essentially all of the circulating active HMG-CoA reductase inhibitors and most (>94%) of the total inhibitors were accounted for by rosuvastatin. Erythromycin did not affect the proportion of circulating active or total inhibitors accounted for by circulating rosuvastatin.

Conclusions: Erythromycin did not produce any increase in rosuvastatin plasma exposure. This indicates that CYP3A4 metabolism is not an important clearance mechanism for rosuvastatin, a result consistent with previous findings. The small decreases in rosuvastatin AUC((0-t)) and C(max) that occurred as a consequence of short-term treatment with erythromycin are unlikely to have relevance to long-term treatment with rosuvastatin.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Bacterial Agents / pharmacology*
  • Area Under Curve
  • Cross-Over Studies
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / metabolism
  • Double-Blind Method
  • Drug Interactions
  • Erythromycin / pharmacology*
  • Fluorobenzenes / pharmacokinetics*
  • Half-Life
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
  • Male
  • Metabolic Clearance Rate
  • Pyrimidines*
  • Rosuvastatin Calcium
  • Sulfonamides*

Substances

  • Anti-Bacterial Agents
  • Cytochrome P-450 Enzyme Inhibitors
  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • Erythromycin
  • Rosuvastatin Calcium
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human