李鑫 1,2,3, 徐晓勇 4,陈渊成 3,5* (1 复旦大学附属华山医院抗生素研究所, 上海, 200040; 2 卫健委抗生素临床药理重点实验室, 上海, 200040; 3 国家老年疾病临床医学研究中心, 上海, 200040; 4 浙江医药股份有限公司, 绍兴, 312366; 5 复旦大学附属华山医院一期临床研究室, 上海, 200040) (* 通讯作者: 联系电话: 021-54602085, Email: cyc_1983@163.com) (第一作者: 联系电话: 021-52888193, Email: lxxj6311@163.com) 表 1:多剂口服不同剂量奈诺沙星药动学参数 注: R 蓄积系数 MIC: 最低抑菌浓度 图 1:奈诺沙星对肺炎链球菌(左图)和金黄色葡萄球菌(右图)的 MIC 分布及其 fAUC0-24/MIC 达标概率 (PTA) 曲线 [实线和虚线分别代表靶值取 35(菌落计数降至基线 10%) 和 47(菌落计数降至基线 1‰), 柱状图表示 MIC 分布频率,水平虚线表示 90% 达标概率) a 包括中性粒细胞百分比或计数降低和中性粒细胞减少症 b 包括白细胞计数减少和白细胞减少症 c 包括 QT 间期延长和校正 QT 间期延长 d 包括血小板计数增加和血小板增多症 参考文献: [1] Zhang J., Zhou L., Yang Y., et al., Therapeutic and triage strategies for 2019 novel coronavirus disease in fever clinics. Lancet Respir Med, Published Online February 13, 2020 https:///10.1016/ S2213-2600(20)30071-0. [2] 武晓捷. 抗菌新药苹果酸奈诺沙星胶囊群体药代动力学及药代动力学/药效学研究 [D]. 复旦大学, 2012. [3] 朱德妹, 吴培澄, 胡付品, 等. 奈诺沙星体外抗菌作用研究 [J]. 中国感染与化疗杂志, 2015(02): 97-112. [4] Wang N., Liu W., Zhou Y., et al., In vitro activities of nemonoxacin and other antimicrobial agents against human Mycoplasma and Ureaplasmas isolates and their defined resistance mechanisms[J]. Front Microbiol. 2019, 10: 1890. [5] 评价口服苹果酸奈诺沙星对比左氧氟沙星治疗成人社区获得性肺炎患者的有效性和安全性的多中心、随机、双盲双模拟、平行对照 III 期临床研究报告, 2012. [6] Liu Y., Zhang Y., Wu J., et al., A randomized, double-blind, multicenter Phase II study comparing the efficacy and safety of oral nemonoxacin with oral levofloxacin in the treatment of community-acquired pneumonia[J]. J Microbiol Immunol Infect, 2017, 50(6): 811-820. [7] Liang W., Chen Y., Cao Y., et al., Pharmacokinetics and pharmacodynamics of nemonoxacin against Streptococcus pneumoniae in an in vitro infection model[J]. Antimicrob Agents Chemother, 2013, 57(7):2942-2947. [8] David H. W, Gigi H.B, Marnie L. P, et al. Application of fluoroquinolone pharmacodynamics[J]. J Antimicrob Chemother, 2000, 46:669-683. [9] 陈渊成. 数学模型与计算机仿真技术在喹诺酮抗菌新药临床研究中的应用. 复旦大学. 博士后研究工作报告. 2013. [10] Zhao C., Lv Y., Li X., et al., Effects of nemonoxacin on thorough ECG QT/QTc interval: a randomized, placebo- and positive-controlled crossover study in healthy Chinese adults[J]. Clin Ther, 2018. 40(6): 983-992. [11] Yuan J., Mo B., Ma Z., et al., Safety and efficacy of oral nemonoxacin versus levofloxacin in treatment of community-acquired pneumonia: a phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled, non- inferiority trial [J]. J Microbiol Immunol Infect, 2019. 52(1): 35-44. [12] Cheng S., Wu R., Chuang Y., et al. Integrated safety summary of phase II and III studies comparing oral nemonoxacin and levofloxacin in community- acquired pneumonia[J]. J Microbiol Immunol Infect, 2019, 52(5): 743-751. |
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