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.
Nilsen
O G
OG
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Trondheim, Norway.
Aamo
T
T
Zahlsen
K
K
Svarva
P
P
D000284:Administration, Oral; D000328:Adult; D001681:Biological Assay; D002851:Chromatography, High Pressure Liquid; D017291:Clarithromycin; D004305:Dose-Response Relationship, Drug; D004917:Erythromycin / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D008297:Male; D011897:Random Allocation; D015575:Roxithromycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets
D013607:Tablets; D015575:Roxithromycin; D004917:Erythromycin; D017291:Clarithromycin