A study of the interaction potential of azithromycin and clarithromycin with atorvastatin in healthy volunteers.
Atorvastatin is a common option among the HMG-CoA reductase inhibitors for the treatment of lipid disorders because of its excellent lipid-lowering efficacy and overall safety profile. Although these agents can rarely cause rhabdomyolysis by themselves, macrolides, among other agents, have been demonstrated to increase the likelihood of this via inhibition of CYP metabolism of the lipid agent. This study investigated the potential for azithromycin and clarithromycin to inhibit the metabolism of atorvastatin. Although there was no interaction between azithromycin and atorvastatin, clarithromycin did have a significant effect on atorvastatin pharmacokinetic parameters. When coadministered, clarithromycin raised subject exposure (AUC24) by 82% and peak plasma concentrations by 56%. These data suggest that while azithromycin appears to be safe to coadminister with atorvastatin, clarithromycin should be avoided in patients taking this and similarly metabolized HMG-CoA inhibitors.
Amsden
Guy W
GW
Clinical Pharmacology Research Center, Research Institute and Department of Medicine, Bassett Healthcare, Cooperstown, New York 13326, USA.
Kuye
Olatunde
O
Wei
Greg C G
GC
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood; D019540:Area Under Curve; D000069059:Atorvastatin; D017963:Azithromycin / Q000097:blood*; D017291:Clarithromycin / Q000097:blood*; D016001:Confidence Intervals; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D064368:Healthy Volunteers; D006538:Heptanoic Acids / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000097:blood*
D000900:Anti-Bacterial Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D017963:Azithromycin; D000069059:Atorvastatin; D017291:Clarithromycin