PharmGKB summary: Macrolide antibiotic pathway, pharmacokinetics/pharmacodynamics
Macrolides are divided into categories on the basis of chemical structure. Erythromycin and clarithromycin are 14-membered lactone rings. Clarithromycin (6-O-methylerythromycin) differs from erythromycin by a methoxy group instead of a hydroxyl group at position 6 on the carbon ring 2. Azithromycin (9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin) is a part of the azalide subclass and contains a 15-membered ring, with a methyl-substituted nitrogen instead of a carbonyl group at the 9a position on the aglycone ring, which prevents metabolism by the mechanism undergone by other macrolides 2,4. Erythromycin was the first macrolide discovered and has been in use since the 1950s, whereas clarithromycin and azithromycin were approved more recently by the Food and Drug Administration in 1991 and 1992, respectively 2,5. Because of its structural differences, azithromycin does not interact with CYP3A4, SLCO1B1, or SLCO1B3, and therefore, has a longer half-life and fewer drug interactions than other macrolides 6,7.
As erythromycin, clarithromycin, and azithromycin are the most commonly described macrolide antibiotics, this review will focus on the pharmacokinetics, pharmacodynamics, and pharmacogenomics of these three drugs (Fig. 1). Zuckerman et al. 2 and Periti et al.1 provide an overview of the pharmacokinetics and pharmacodynamics of other macrolides, such as telithromycin, tigecycline, and roxithromycin.