Pharmacokinetics and Pharmacodynamics of Multiple-Dose Intravenous Nemonoxacin in Healthy Chinese Volunteers Xiao-jie Wu,a,b Jing Zhang,a,b Bei-ning Guo,a,b Ying-yuan Zhang,a,b Ji-cheng Yu,a,b Guo-ying Cao,a,b Yuan-cheng Chen,a,b De-mei Zhu,a Xin-yu Ye,a,b Ju-fang Wu,a,b Yao-guo Shi,a,b Li-wen Chang,c Yu-ting Chang,c Cheng-yuan Tsaic
This study evaluated the safety and pharmacokinetic/pharmacodynamic profiles of nemonoxacin in healthy Chinese volunteers following multiple-dose intravenous infusion once daily for 10 consecutive days. The study was composed of two stages. In the open-label stage, 500 mg or 750 mg of nemonoxacin (n ⴝ 12 each) was administered at an infusion rate of 5.56 mg/min. In the second stage, with a randomized double-blind placebo-controlled design, 500, 650, or 750 mg of nemonoxacin (n ⴝ 16 in each cohort; 12 subjects received the drug and the other 4 subjects received the placebo) was given at an infusion rate of 4.17 mg/min. The results showed that, in the first stage, the maximal nemonoxacin concentrations (mean ⴞ SD) at steady state (Cmax_ss) were 9.60 ⴞ 1.84 and 11.04 ⴞ 2.18 g/ml in the 500-mg and 750-mg cohorts, respectively; the areas under the concentration-time curve at steady state (AUC0 –24_ss) were 44.03 ⴞ 8.62 and 65.82 ⴞ 10.78 g · h/ml in the 500-mg and 750-mg cohorts, respectively. In the second stage, the nemonoxacin Cmax_ss values were 7.13 ⴞ 1.47, 8.17 ⴞ 1.76, and 9.96 ⴞ 2.23 g/ml in the 500-mg, 650-mg, and 750-mg cohorts, respectively; the AUC0 –24_ss values were 40.46 ⴞ 9.52, 54.17 ⴞ 12.10, and 71.34 ⴞ 17.79 g · h/ml in the 500mg, 650-mg, and 750-mg cohorts, respectively. No accumulation was found after the 10-day infusion with any regimen. The drug was well tolerated. A Monte Carlo simulation indicated that the cumulative fraction of response of any dosing regimen was nearly 100% against Streptococcus pneumoniae. The probability of target attainment of nemonoxacin therapy was >98% when the MIC of nemonoxacin against S. pneumoniae was
This study evaluated the safety and pharmacokinetic/pharmacodynamic profiles of nemonoxacin in healthy Chinese volunteers following multiple-dose intravenous infusion once daily for 10 consecutive days. The study was composed of two stages. In the open-label stage, 500 mg or 750 mg of nemonoxacin (n ⴝ 12 each) was administered at an infusion rate of 5.56 mg/min. In the second stage, with a randomized double-blind placebo-controlled design, 500, 650, or 750 mg of nemonoxacin (n ⴝ 16 in each cohort; 12 subjects received the drug and the other 4 subjects received the placebo) was given at an infusion rate of 4.17 mg/min. The results showed that, in the first stage, the maximal nemonoxacin concentrations (mean ⴞ SD) at steady state (Cmax_ss) were 9.60 ⴞ 1.84 and 11.04 ⴞ 2.18 g/ml in the 500-mg and 750-mg cohorts, respectively; the areas under the concentration-time curve at steady state (AUC0 –24_ss) were 44.03 ⴞ 8.62 and 65.82 ⴞ 10.78 g · h/ml in the 500-mg and 750-mg cohorts, respectively. In the second stage, the nemonoxacin Cmax_ss values were 7.13 ⴞ 1.47, 8.17 ⴞ 1.76, and 9.96 ⴞ 2.23 g/ml in the 500-mg, 650-mg, and 750-mg cohorts, respectively; the AUC0 –24_ss values were 40.46 ⴞ 9.52, 54.17 ⴞ 12.10, and 71.34 ⴞ 17.79 g · h/ml in the 500mg, 650-mg, and 750-mg cohorts, respectively. No accumulation was found after the 10-day infusion with any regimen. The drug was well tolerated. A Monte Carlo simulation indicated that the cumulative fraction of response of any dosing regimen was nearly 100% against Streptococcus pneumoniae. The probability of target attainment of nemonoxacin therapy was >98% when the MIC of nemonoxacin against S. pneumoniae was
