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 pharmacokine tics of oral moxifloxacin in healthy adult male volunteers. Design and setting: This was a nonblinded, randomised, 2-way crossover stud y. Patients and participants: 12 male Caucasian volunteers (mean age 33.7 year s) 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 da ily starting at 1 hour before the moxifloxacin dose. There was a washout ph ase of at least 1 week between the 2 treatments. Samples of plasma and urin e were taken according to predefined sampling schedules and the concentrati ons of moxifloxacin were determined with a validated high performance liqui d chromatography assay with fluorescence detection. Noncompartmental pharma cokinetic data were calculated. Results: Pharmacokinetic results with and without probenecid were virtually identical except for a slight delay in absorption with probenecid, indicat ed by a very slightly increased time to maximum concentration and a decreas ed maximum concentration (approximately 10%), which was not clinically rele vant. Probenecid had no significant influence on the renal elimination of m oxifloxacin, suggesting urinary excretion by glomerular filtration and part ial tubular reabsorption. Safety and tolerability were good, with no clinic ally relevant drug-related adverse events or changes in laboratory paramete rs. Conclusion: Dosage adjustments for moxifloxacin are not necessary when it i s administered together with probenecid.