Erythromycin coadministration increases plasma atorvastatin concentrations

The effect of erythromycin on the pharmacokinetics of atorvastatin, an inhi bitor of HMG-CoA reductase, was investigated in 12 healthy volunteers. Each subject received a single 10 mg dose of atorvastatin on two separate occas ions, separated by 2 weeks. Erythromycin (500 mg qid) was given from 7 days before through 4 days after the second atorvastatin dose. Atorvastatin con centrations were determined by an enzyme inhibition assay; which measured b oth atorvastatin and active metabolites. When erythromycin was coadminister ed with atorvastatin, mean C-max and AUC((0-infinity)) increased by 37.7% a nd 32.5%, respectively. Mean terminal half-life was similar following each atorvastatin dose. Possible mechanisms for this interaction include erythro mycin inhibition of first-pass conversion of atorvastatin to inactive metab olites and erythromycin inhibition of P-glycoprotein-mediated intestinal or biliary secretion. (C) 1999 the American College of Clinical Pharmacology.