The influence of age and gender on the pharmacokinetics of moxifloxacin

Objective: Moxifloxacin is a new 8-methoxyfluoroquinolone with a broad anti bacterial spectrum. The purpose of the present study was to determine the e ffects of age and gender on pharmacokinetics, surrogate pharmacodynamics. s afety and tolerability of a single dose of moxifloxacin. Design: This was a randomised, double-blind, placebo-controlled, parallel-g roup single dose trial in young and elderly healthy volunteers. Patients and participants: The study included 36 volunteers in 3 age and ge nder groups: young males (mean age 32 years), elderly males (mean age 74 ye ars), and elderly females (mean age 74 years). Methods: Participants received either a single 200mg oral dose of moxifloxa cin (8/group) or placebo (4/group). Blood samples for moxifloxacin pharmaco kinetics were obtained before and up to 48 hours after administration. Urin e samples were collected for pharmacokinetics, and volunteers were monitore d for clinical adverse events and laboratory abnormalities. Results: Maximum plasma concentration (C-max) and area under the plasma con centration-time curve (AUC) were higher in elderly females than in elderly males; however, when normalised for bodyweight, these pharmacokinetic param eters were not significantly different between the groups. Moreover, the pl asma pharmacokinetics in elderly males were not meaningfully different from those in young males. Elimination half-life averaged 12 to 13 hours for th e 3 groups. Surrogate pharmacodynamic measures were derived using AUC/MIC ( minimal inhibitory concentration) and C-max/MIC ratios. These assessments i ndicated that, given the linear pharmacokinetics of moxifloxacin previously demonstrated, a dose of 400mg would produce mean C-max/MIC values in the d ifferent subgroups ranging from 10.4 to 15.4 for an MIC of 0.25, and 20.8 t o 30.8 for an MIC of 0.125. The corresponding ranges of projected AUC/MIC r atios would be 112 to 158 for an MIC of 0.25, and 224 to 314 for an MIC of 0.125. The accepted target values of AUC/MIC and C-max/MIC for quinolones a re 125 and 10, respectively. There were no serious adverse events or differ ences in adverse event profiles between the groups. Conclusions: Moxifloxacin does not exhibit age- or gender-dependent pharmac okinetics. Oral doses of 200 to 400mg yield effective antibacterial concent rations on the first day of administration.