Pharmacokinetics of a once-daily oral dose of moxifloxacin (Bay 12-8039), a new enantiomerically pure 8-methoxy quinolone

The pharmacokinetics, safety, and tolerability of oral moxifloxacin, a new 8-methoxy quinolone, were assessed in a randomized, double-blind, placebo-c ontrolled study in which healthy male and female volunteers received either 400 mg of moxifloxacin once daily (n = 10) or a placebo once daily (n = 5) for 10 days. Plasma moxifloxacin concentrations an days 1 and 10 were meas ured by high-performance liquid chromatography and fluorometric detection. Standard pharmacokinetic parameters were estimated by noncompartmental meth ods. Natural logarithmic estimates for each pharmacokinetic variable of eac h subject were analyzed by a two-way analysis of variance. Hematology, bloo d chemistry, vital signs, and adverse events were monitored, and electrocar diograms (ECG) were performed. Plasma moxifloxacin concentrations of predic ted therapeutic relevance were achieved in this study. For day 1, the mean maximum concentration of drug in serum (C-max) and the area under the conce ntration-time curve from 0 to 24 h (AUC(0-24)) were 3.4 mg/liter and 30.2 m g.h/liter, respectively. Corresponding means on day 10 were 4.5 mg/liter an d 48 mg.h/liter, respectively. On day 10, the mean elimination half-life wa s approximately 12 h. Plasma moxifloxacin concentrations exceeded the MIC f or Streptococcus pneumoniae throughout the 24-h dosing period. The day 1 an d day 10 mean AUC/MIC ratios were 121 and 192, respectively, and the mean C -max/MIC ratios were 13 and 18, respectively. Moxifloxacin was well tolerat ed; no clinically relevant changes in the standard laboratory tests, vital signs, or ECG were observed. Pharmacokinetic parameters demonstrated linear ity, and estimates of pharmacokinetic/pharmacodynamic ratios (AUC/MIC and C -max/MIC) indicate that the regimen of 400-mg once daily should be effectiv e for treating a variety of infections. Moxifloxacin was found to be safe a nd,well tolerated in healthy volunteers when it was given as a single daily 400-mg dose for 10 days.