title: Pharmacokinetics and pharmacodynamics of multiple-dose intravenous nemonoxacin in healthy Chinese volunteers.
abstract: 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 = 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 = 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 ± SD) at steady state (Cmax_ss) were 9.60 ± 1.84 and 11.04 ± 2.18 μg/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 ± 8.62 and 65.82 ± 10.78 μg · h/ml in the 500-mg and 750-mg cohorts, respectively. In the second stage, the nemonoxacin Cmax_ss values were 7.13 ± 1.47, 8.17 ± 1.76, and 9.96 ± 2.23 μg/ml in the 500-mg, 650-mg, and 750-mg cohorts, respectively; the AUC0-24_ss values were 40.46 ± 9.52, 54.17 ± 12.10, and 71.34 ± 17.79 μg · h/ml in the 500-mg, 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 ≤1 mg/liter. It is suggested that all of the studied intravenous nemonoxacin dosing regimens should have favorable clinical and microbiological efficacies in future clinical studies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01944774.).
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Xiao-jie
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China zhangj_fudan@aliyun.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Bei-ning
authors.initials: BN
authors.lastname: Guo
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Ying-yuan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Ji-cheng
authors.initials: JC
authors.lastname: Yu
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Guo-ying
authors.initials: GY
authors.lastname: Cao
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Yuan-cheng
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: De-mei
authors.initials: DM
authors.lastname: Zhu
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Xin-yu
authors.initials: XY
authors.lastname: Ye
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Ju-fang
authors.initials: JF
authors.lastname: Wu
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Yao-guo
authors.initials: YG
authors.lastname: Shi
authors.affiliation: TaiGen Biotechnology Co., Ltd., Taipei, Taiwan.
authors.forename: Li-wen
authors.initials: LW
authors.lastname: Chang
authors.affiliation: TaiGen Biotechnology Co., Ltd., Taipei, Taiwan.
authors.forename: Yu-ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: TaiGen Biotechnology Co., Ltd., Taipei, Taiwan.
authors.forename: Cheng-yuan
authors.initials: CY
authors.lastname: Tsai
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009010:Monte Carlo Method; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D015363:Quinolones; C543520:nemonoxacin