Pharmacokinetic and pharmacodynamic aspects of oral moxifloxacin 400 mg/day in elderly patients with acute exacerbation of chronic bronchitis

OBJECTIVE: To assess the pharmacokinetic and pharmacodynamic behaviour of moxifloxacin in 15 consecutive elderly patients with acute exacerbation of chronic bronchitis (AECB) treated with the fixed oral moxifloxacin 400 mg/day regimen with the intent of verifying which degree of exposure may be ensured by this standard regimen against AECB pathogens. METHODS: This was an open-label, observational, pharmacokinetic-pharmacodynamic study. Blood samples were collected at steady state at appropriate intervals. Moxifloxacin plasma concentrations were analysed by means of high-performance liquid chromatography. Standard pharmacokinetic parameters and pharmacodynamic determinants (peak concentration [C(max)]/minimum inhibitory concentration [MIC], area under the plasma concentration-time curve during the 24-hour observational period [AUC(24)]/MIC, pharmacodynamic breakpoints [PDBPs]) were assessed. RESULTS: The mean estimated pharmacokinetic parameters (C(max) 4.40 mg/L at 1.4 hours, AUC(24) 42.67 mg . h/L, elimination half-life 12.55 hours, total body clearance 0.16 L/h/kg) were generally similar to those observed in both young and elderly historic controls (except for higher-dose normalised C(max) and lower volume of distribution of the central compartment). Median C(max)/MIC and AUC(24)/MIC ratios for moxifloxacin in the fully assessable cases were, respectively, 67.5 and 823.9 against Streptococcus pneumoniae, 25 and 310.2 against Moraxella catharralis and 416.5 and 3647.5 against Haemophilus influenzae. Mean estimates of PDBP for achieving C(max)/MIC values of 12.2 and AUC(24)/MIC values of 125 were 0.36 and 0.35 mg/L, respectively. CONCLUSION: In patients with AECB the pharmacokinetic behaviour of moxifloxacin is not significantly altered by aging processes. This is consistent with moxifloxacin being metabolised mainly by means of phase II hepatic reactions, the activity of which was shown not to decline with age. Both the pharmacokinetic and pharmacodynamic analyses suggest that moxifloxacin 400 mg/day may be a valid therapeutic approach in the treatment of AECB in the elderly. Of note, the unmodified pharmacokinetic behaviour with no need for age-related dosage adjustments combined with the once-daily administration favouring compliance and the low potential for drug-drug pharmacokinetic interactions in case of polytherapy, make moxifloxacin particularly attractive in the treatment of elderly subpopulations at a very high risk of AECB