单次静滴注射用头孢他美钠Ⅰ期临床试验  

PhaseⅠ Clinical Trial on the Safety of Injectable Cefetamet Sodium with a Single Dose in Healthy Volunteers

作　　者：李才正[1] 孙家钰[1] 王颖[1] 秦永平[1] 苗佳[1] 

机构地区：[1]四川大学华西医院I期临床研究室,成都610041

出　　处：《四川大学学报（医学版）》2014年第4期637-641,共5页Journal of Sichuan University(Medical Sciences)

摘　　要：目的通过Ⅰ期临床试验,考察中国健康志愿者接受单次静滴注射用头孢他美钠的安全性,确定最大耐受剂量,并了解其药代动力学特征。方法选择60名健康志愿者参加Ⅰ期临床耐受性试验,试验采用随机、双盲、安慰剂平行对照设计,按剂量递增原则从100~5 000mg共设8个剂量组,逐组完成单次用药的安全性观察。药代动力学研究采用拉丁方三交叉自身对照试验设计,12名健康志愿者分别先后单次恒速静滴500mg、1 000mg、2 000mg注射用头孢他美钠,采用HPLC-UV法测定血样中头孢他美的浓度,经DAS2.0程序处理得到主要药代动力学参数。结果 59例健康受试者完成了Ⅰ期耐受性试验,给药组和安慰剂组临床不良反应发生率分别为22.73%和6.67%,两组差异无统计学意义（P〉0.05）,给药组常见临床不良反应有输注部位疼痛、头晕,少见临床不良反应有心悸、腹泻及皮疹,均为轻度。实验室检查结果异常的发生率分别为43.18%和53.33%,两组比较差异无统计学意义（P〉0.05）,给药组常见实验室检查异常为大便菌群比例异常、大便常规异常、尿常规异常、血钾升高等。药代动力学试验发现,单次静滴本品0.5h后即刻达峰浓度（Cmax）,500mg、1 000mg、2 000mg的Cmax分别为（37.92±7.43）、（74.90±10.67）、（148.54±31.63）mg/L,药时曲线下面积（AUC0~t）分别为（72.08±14.98）、（144.28±24.57）、（286.66±54.25）（mg·h）/L,消除半衰期（t1/2）分别为（2.03±0.38）、（2.04±0.26）、（2.12±0.26）h。其体内过程符合二室模型,并呈线性动力学特征。0~24h尿药累积排泄率为76.6%~67.5%。结论注射用头孢他美钠单次给药最大耐受剂量为5 000mg,500~2 000mg的药代动力学符合二室模型,并具有线性动力学特征。Objective To investigate the safety and maximum tolerable dosage of injectable cefetamet sodium with a single infusion in Chinese healthy volunteers.Methods Sixty healthy volunteers were enrolled in this study.A double-blinded,randomized,placebo-controlled design was adopted.Eight dosages ranging from 100 mg to5 000mg were tested.The pharmacokinetics of the drug was analyzed using a Latin square three-cross selfcontrolled design,with 12healthy volunteers receiving 500mg,1 000mg and 2 000mg of injectable cefetamet sodium in a randomized sequence.Blood and urine samples were collected and analyzed using high performance liquid chromatography with UV detection.The main pharmacokinetics parameters were calculated with DAS2.0software.Results 59healthy volunteers completed the tolerance tests.Clinical adverse reactions occurred in 22.73% of participants in the test group and 6.67%of participants in the placebo group;but the difference was not statistically significant.Common adverse events included infusion pain and dizziness.Rare adverse events such as palpitations,diarrhea and rash occurred in participants in the test group.All of the adverse reactions were mild.Abnormal laboratory test results occurred in 43.18% participants in the test group and 53.33% participants in the placebo group;again the difference was not statistically significant.Common abnormal laboratory test results included abnormal bowel flora,stool abnormalities,abnormal urine and elevated serum potassium.After a single infusion of500mg,1 000mg and 2 000mg of injectable cefetamet sodium,peak concentration of the drug at 0.5hreached（37.92±7.43）,（74.90±10.67）and（148.54±31.63）mg/L,with areas under concentration-time curve of（72.08±14.98）,（144.28±24.57）and（286.66±54.25）（mg·h）/L,respectively.Their elimination half-life was（2.03±0.38）,（2.04±0.26）,and（2.12±0.26）h,respectively.The disposition of cefetamet was presented as a two-compartment model with linear kinetics.The 24-hour urinary accumulation excretion

关 键 词：注射用头孢他美钠 耐受性 药代动力学 健康志愿者 

分 类 号：R969.4[医药卫生—药理学]