title: Single- and multiple-dose pharmacokinetics of oral moxifloxacin and clarithromycin, and concentrations in serum, saliva and faeces.
abstract: Moxifloxacin and clarithromycin are important antibacterial drugs in the treatment of community-acquired respiratory tract infections. In a double-blind, randomized, 2-period cross-over study the pharmacokinetics of moxifloxacin versus clarithromycin were determined after single and multiple doses in 12 healthy male volunteers. The concentrations of the antibiotics in serum, saliva and faeces were measured by validated high-performance liquid chromatographic methods. In serum, moxifloxacin exhibited a mean peak concentration of 3.1 +/- 0.6 mg/l after a time to peak concentration of 1.67 +/- 0.96 h on day 1, with a significant increase to 3.98 +/- 1.10 mg/l on day 7 (p < 0.05). The area under the curve-12 revealed a highly significant increase from 28.2 + 4.1 mg*h/l on day 1 to 39.5 +/- 6.6 mg*h/l on day 7 (p < 0.01). There were also significant differences in terminal half-life between day 1 and day 7 [10.6 h (range 9.0-12.8) vs 14.9 h (range 12.6-28.1); p < 0.01] and in mean residence time (15.1 +/- 1.9 vs 18.2 +/- 2.4 h; p < 0.01). The concentrations of moxifloxacin in saliva were well equilibrated with serum at a relatively constant saliva-serum ratio of about 0.8. Pharmacokinetic parameters of clarithromycin and its metabolite, 14-hydroxy-clarithromycin, were similar to previously published data. Accumulation was found. No serious adverse events were observed with either study drug.
authors.affiliation: Department of Chest and Infectious Diseases, Hospital Heckeshorn, Berlin, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Burkhardt
authors.forename: Klaus
authors.initials: K
authors.lastname: Borner
authors.forename: Heino
authors.initials: H
authors.lastname: Stass
authors.forename: Gerrit
authors.initials: G
authors.lastname: Beyer
authors.forename: Markus
authors.initials: M
authors.lastname: Allewelt
authors.forename: Carl Erik
authors.initials: CE
authors.lastname: Nord
authors.forename: Hartmut
authors.initials: H
authors.lastname: Lode
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001372:Aza Compounds; D017291:Clarithromycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005243:Feces / Q000737:chemistry* / Q000382:microbiology; D024841:Fluoroquinolones; D006207:Half-Life; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000382:microbiology; D008297:Male; D008657:Metabolic Clearance Rate; D000077266:Moxifloxacin; D009960:Oropharynx / Q000187:drug effects / Q000382:microbiology; D011804:Quinolines; D012463:Saliva / Q000378:metabolism* / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; C056228:14-hydroxyclarithromycin; D017291:Clarithromycin; D000077266:Moxifloxacin