Effect of probenecid on the kinetics of a single oral 400mg dose of moxifloxacin in healthy male volunteers.
OBJECTIVE
To investigate the effect of oral probenecid on the pharmacokinetics of oral moxifloxacin in healthy adult male volunteers.


METHODS
This was a nonblinded, randomised, 2-way crossover study.


METHODS
12 male Caucasian volunteers (mean age 33.7 years) participated in the study.


METHODS
A single oral dose of moxifloxacin 400mg was administered after an overnight fast with or without a 2-day course of probenecid 500mg twice daily starting at 1 hour before the moxifloxacin dose. There was a washout phase of at least 1 week between the 2 treatments. Samples of plasma and urine were taken according to predefined sampling schedules and the concentrations of moxifloxacin were determined with a validated high performance liquid chromatography assay with fluorescence detection. Noncompartmental pharmacokinetic data were calculated.


RESULTS
Pharmacokinetic results with and without probenecid were virtually identical except for a slight delay in absorption with probenecid, indicated by a very slightly increased time to maximum concentration and a decreased maximum concentration (approximately 10%), which was not clinically relevant. Probenecid had no significant influence on the renal elimination of moxifloxacin, suggesting urinary excretion by glomerular filtration and partial tubular reabsorption. Safety and tolerability were good, with no clinically relevant drug-related adverse events or changes in laboratory parameters.


CONCLUSIONS
Dosage adjustments for moxifloxacin are not necessary when it is administered together with probenecid.
Stass
H
H
Pharma Research Centre, Institute of Clinical Pharmacology, Bayer AG, Wuppertal, Germany. Heino.Stass.hs@bayer-ag.de
Sachse
R
R
D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001372:Aza Compounds; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004347:Drug Interactions; D024841:Fluoroquinolones; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D000077266:Moxifloxacin; D011339:Probenecid / Q000494:pharmacology*; D011804:Quinolines; D014528:Uricosuric Agents / Q000494:pharmacology*
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D014528:Uricosuric Agents; D011339:Probenecid; D000077266:Moxifloxacin