000000f9_李苌清-抗生素.docVIP

基于PK-PD研究确定头孢曲松舒巴坦Ⅱ期临床给药方案 李苌清1, 陈昭丽2，王广基3, 王 霆1,4( （1广州威尔曼新药研发有限公司，广州 510075；2中南大学药学院药物分析教研室，长沙410013湘北威尔曼制药有限公司，长沙410329[中图分类号] R969.1 [文献标识码] A Use of preclinical and phaseⅠ data for determing a phaseⅡ dose for ceftriaxone/sulbactam injection LI Chang-qing1，CHEN Zhao-li2 WANG Guang-ji3, WANG Ting1,4 （1 Guangzhou Welman New Drug R D Co., Ltd, Guangzhou ,510075,China;2 Department of Pharmaceutical Analysis, College of Pharmacy, Central South University, Changsha, 410013；3 China Pharmaceutical University,Naijing 21009,China；4 Xiangbei Welman Pharmaceutical Co.Ltd, Changsha , 410329) [Abstract] Objective：To select a PhaseⅡ Dose for ceftriaxone/sulbactam injection by Monte Carlo Simulation using Preclinical and PhaseⅠ Data. Methods：Pharmacodynamic data (MICs) were obtained from Pre-clinical studies. Pharmacokinetic data from Phase Ⅰ clinical research trials and published protein binding were varied according to log-normal and uniform distributions. A Monte Carlo simulation (10,000 subjects) estimated the probability of target attainment (PTA)and cumulative fraction of response (CFR) for drug concentrations at 50% T(MIC) for ceftriaxone 0.5-2.5 g intravenously every 8-24 h. A CFR or =90% was considered microbiologic success. Resluts: A CFR＞or =90% against key extended-spectrum β-lactamase-producing Enterobacteriaceae was predicted for 2.2g q24h, 1.3g q12h and 1.1g q8h. Conclusion：The 1.3g q12h regimen is an appropriate dose for PhaseⅡ of ceftriaxone/sulbactam injection, based on its PK/PD characteristics, safety and cost effective. [Key words] ceftriaxone/sulbactam; Monte Carlo simulation; pharmacokinetics; pharmacodynamics [中图分类号] R969.1 [文献标识码] B 注射用头孢曲松钠舒巴坦钠（2:1））））MIC values of ceftriaxone-sulbactam (2:1) againstβ-lactamase-producing strains. / Proteus MIC (mg/L) Escherichia coli Klebsiella pneumoniae Citrobacter sp. Serratia sp. Proteus sp. MIC50 4 4 8 8 4 MIC90 16 16 16 16 32 MICrange 0.25-32 0.25-64 0.5-64 0.25-32 2-64 2 药代动力学研究 第四军医大学国家药品临床研究机构顾宜