Macrolide pharmacokinetics and dose scheduling of roxithromycin

The 150- and 300-mg single-dose pharmacokinetics of roxithromycin were investigated in 12 healthy subjects in a crossover study. Serum concentrations were determined by high-performance liquid chromatography (HPLC) and microbiologic assay (MA). Peak serum levels as measured by HPLC were 6.7 +/- 2.6 (150 mg) and 11.0 +/- 2.2 micrograms/ml (300 mg) and did not differ significantly from the values obtained by MA. Mean serum roxithromycin levels 12 hr after the 150-mg dose and 24 hr after the 300-mg dose were 2.50 and 2.55 micrograms/ml, respectively. HPLC analysis of a comparable macrolide, clarithromycin, showed peak serum levels of 1.2 +/- 0.6 and 2.3 +/- 0.6 micrograms/ml after oral dosing with 250 and 500 mg in the same subjects. The 14-OH metabolite reached a level that was 50% and 40%, respectively, of that of the parent compound. Roxithromycin showed a prolonged elimination half-life compared with clarithromycin and its 14-OH metabolite. Mean values of 14.6, 3.5, and 5.5 hr, respectively, indicate the need for less frequent dosing of roxithromycin.