头孢噻肟钠他唑巴坦钠注射液静脉滴注在健康志愿者的临床药代动力学研究及其算法探讨  

Study on Pharmacokinetics and algorithm of cefotaxime sodium tazobactam sodium for intravenous drip in healthy volunteers

作　　者：许羚[1] 盛玉成[1] 郑青山[1] 

机构地区：[1]安徽省药物临床评价中心,皖南医学院弋矶山医院

出　　处：《中国临床药理学与治疗学》2005年第11期1225-1230,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：安徽省优秀青年科技基金项目(№04043052);安徽省临床医学重点学科技术进步专项基金项目(№20042035)

摘　　要：目的:研究头孢噻肟钠他唑巴坦钠(31)注射液单次和多次静脉滴注在健康志愿者中的药代动力学和安全性。方法:男女各半的32名受试者随机分为3个单次给药剂量组和一个多次给药剂量组。用药后采用高效液相色谱法和液-质联用分别测定4组受试者不同时间点两种药物的血药浓度以及单次给药中剂量组的尿药中两种药物的浓度。经DAS软件处理后,求出其药动学参数。结果:受试者用药后头孢噻肟钠、他唑巴坦钠均符合二室模型。单剂量给药6.0、2.4、1.2g剂量组头孢噻肟钠t12β分别为2.53±1.51、2.23±1.18、2.68±2.65h,MRT0-tn分别为2.1±0.24、1.25±0.19、1.2±0.17h,AUC0-tn分别为312.87±134.15、137.92±39.89、69.18±16.54mg·h·L-1,AUC0-∞分别为318.64±137.4、141.4±40.46、71.26±17.44mg·h·L-1。他唑巴坦钠t12β分别为0.55±0.07、0.48±0.22、0.47±0.28h,MRT0-tn分别为1.56±0.08、0.91±0.07、0.78±0.04h,AUC0-tn分别为64.5±14.69、22.14±8.41、11.9±3.22mg·h·L-1,AUC0-∞分别为66.63±15.33、23.26±8.29、13.64±3.46mg·h·L-1。多次给药组(1.8gtid)头孢噻肟钠和他唑巴坦钠t12β1.5±0.51和0.49±0.14h,AUCss197.23±10.62和30.91±10.78mg·h·L-1,Cav24.65±1.33和3.86±1.35mg·L-1,DF3.92±0.41和4.68±0.59。头孢噻肟钠和他唑巴坦钠药时曲线下面积均与剂量呈线性关系。单次给药中剂量组10h头孢噻肟钠和他唑巴坦钠累计尿排率为49.6±0.58%和80.0±7.0%。结论:头孢噻肟钠他唑巴坦钠(31)静脉滴注给药后两种成分的血清动力学均符合一级消除动力学的二室模型。多次给药后体内无蓄积。头孢噻肟钠部分在肾中代谢,他唑巴坦钠主要从肾中代谢。AIM： To study the pharmacokinetics of cefotaxime sodium tazobactam sodium （3 ： 1 ） after single and multiple intravenous drip in healthy volunteers. METHODS： Thirty two healthy volunteers, half male and half female, were randomly assigned to three groups of single dose and one group of multiple dose. The drag concentration of senml samples after intravenous drip of each dose and urine samples after intravenous drip of a single 2.4g dose were determined by HPLC or HPLC-MS method. The pharmacokinetic parameters were calculated by DAS software. RESULTS： The pharmacokinetics of cefotaxime sodium and tazobactam sodium was fitted into the twocompartment model. After intravenous drip of three single 6.0, 2.4, and 1.2 g dose, the values of t1/2β in cefotaxime sodium were 2.53 ± 1.51, 2.23 ±1.18, and 2.68 ±2.65 h, respectively ; MRT0 were 2.1± 0.24, 1.25 ± 0.19, and 1.2 ± 0.17 h; AUC0-tn, were 312.87 ± 134.15, 137.92 ± 39.89, and 69.18 ±16.54 mg·h·L^-1; AUC0-x were 318.64± 137.4, 141.4± ±0. 46, and 71.26 ± 17.44 mg· h· L^- 1. At the same doses, the values of t1/2β in tazobactam sodium were 0.55 ± 0.07, 0.48 ± 0.22, and 0.47±0.28 h, respectively; MRT0-tn, were 1.56 ± 0.08, 0.91 ± 0.07, and 0.78 ± 0.04 h; AUC0-tn, were 64.5±14.69, 22.14 ± 8.41,and 11.9±3.22 mg·h·L^-1; AUC0-tn were 66.63± 15.33, 23.26 ± 8.29, and 13.64 ±3.46 mg·h·L^-1. After intravenous drip of multiple 1.8 g dose, the values of t1/2β in cefotaxime sodium and tazobactam sodium were 1.5 ± 0.51 and 0.49 ± 0.14 h, respectively; AUCss were 197.23 ±10.62 and 30.91± 10.78 mg·h·L^-1; Cav were 24.65 ± 1.33 and 3.86± 1.35 mg·L^-1 ; DF were 3.92 ± 0.41 and 4.68± 0.59. There was a good linear relationship between AUC and doses of cefotaxime sodium and tazobactam sodium. The cumulative urinary excretion rates of cefotaxime sodium and tazobactam sodi- um were （49.6±0.58）% and （80.0±7.0）% after in- travenous drip of a single 2.4 g dose, respectively. CONCLUSION： The pharmacokinetics of cefotaxime sodiu

关 键 词：头孢噻肟钠 他巴坦钠 药代动力学 房室模型参数 统计矩参数 

分 类 号：R969.1[医药卫生—药理学]