title: In vitro and in vivo activities of macrolides against Mycobacterium leprae.
abstract: We previously demonstrated the potent in vitro activity of erythromycin against Mycobacterium leprae as determined by its effect on ATP pools and rates of palmitate oxidation and phenolic glycolipid I synthesis. In the present study, the relative in vitro activities of a number of new macrolides with superior pharmacokinetic properties were assessed. In addition, for the most active compounds, concentrations in serum were determined by bioassay during continuous administration in the feed of mice, and in vivo activity against M. leprae was assessed by the kinetic mouse footpad technique. Both clarithromycin and roxithromycin were more potent than erythromycin in vitro, with the former showing the highest activity in accelerating rates of ATP decay and reducing rates of palmitate oxidation. In mice, concentrations of clarithromycin in serum were higher than those of roxithromycin and erythromycin, with the latter undetectable even when administered at 0.1% (wt/wt) in the diet. When administered at 0.01% (wt/wt) in the diet, erythromycin and roxithromycin were unable to inhibit growth of M. leprae in mouse footpads whereas clarithromycin demonstrated bactericidal-type activity. On the basis of these data and other properties of macrolides, a clinical trial of clarithromycin in leprosy is warranted.
authors.affiliation: Gillis W. Long Hansen's Disease Center, Carville, Louisiana 70721.
authors.forename: S G
authors.initials: SG
authors.lastname: Franzblau
authors.forename: R C
authors.initials: RC
authors.lastname: Hastings
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004917:Erythromycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D007917:Leprostatic Agents / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D009166:Mycobacterium leprae / Q000187:drug effects*
chemical_list: D007917:Leprostatic Agents; D004917:Erythromycin