The influence of age and gender on the pharmacokinetics of moxifloxacin.

OBJECTIVE

Moxifloxacin is a new 8-methoxyfluoroquinolone with a broad antibacterial spectrum. The purpose of the present study was to determine the effects of age and gender on pharmacokinetics, surrogate pharmacodynamics, safety and tolerability of a single dose of moxifloxacin.

DESIGN

This was a randomised, double-blind, placebo-controlled, parallel-group single dose trial in young and elderly healthy volunteers.

PATIENTS AND PARTICIPANTS

The study included 36 volunteers in 3 age and gender groups: young males (mean age 32 years), elderly males (mean age 74 years), and elderly females (mean age 74 years).

METHODS

Participants received either a single 200mg oral dose of moxifloxacin (8/group) or placebo (4/group). Blood samples for moxifloxacin pharmacokinetics were obtained before and up to 48 hours after administration. Urine samples were collected for pharmacokinetics, and volunteers were monitored for clinical adverse events and laboratory abnormalities.

RESULTS

Maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were higher in elderly females than in elderly males; however, when normalised for bodyweight, these pharmacokinetic parameters were not significantly different between the groups. Moreover, the plasma pharmacokinetics in elderly males were not meaningfully different from those in young males. Elimination half-life averaged 12 to 13 hours for the 3 groups. Surrogate pharmacodynamic measures were derived using AUC/MIC (minimal inhibitory concentration) and Cmax/MIC ratios. These assessments indicated that, given the linear pharmacokinetics of moxifloxacin previously demonstrated, a dose of 400mg would produce mean Cmax/MIC values in the different subgroups ranging from 10.4 to 15.4 for an MIC of 0.25, and 20.8 to 30.8 for an MIC of 0.125. The corresponding ranges of projected AUC/MIC ratios 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 Cmax/MIC for quinolones are 125 and 10, respectively. There were no serious adverse events or differences in adverse event profiles between the groups.

CONCLUSIONS

Moxifloxacin does not exhibit age- or gender-dependent pharmacokinetics. Oral doses of 200 to 400mg yield effective antibacterial concentrations on the first day of administration.