Single- and multiple-dose pharmacokinetics of oral moxifloxacin and clarithromycin, and concentrations in serum, saliva and faeces.
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.
Burkhardt
Olaf
O
Department of Chest and Infectious Diseases, Hospital Heckeshorn, Berlin, Germany.
Borner
Klaus
K
Stass
Heino
H
Beyer
Gerrit
G
Allewelt
Markus
M
Nord
Carl Erik
CE
Lode
Hartmut
H
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
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; C056228:14-hydroxyclarithromycin; D017291:Clarithromycin; D000077266:Moxifloxacin