布洛芬注射液在中国健康受试者中单次和多次给药的药代动力学研究  

Pharmacokinetic study of single dose and multiple doses of ibuprofen injection in healthy Chinese volunteers

作　　者：文元新 陈朝霞 叶薇 南峰 张梅[1] WEN Yuan-xin;CHEN Zhao-xia;YE Wei;NAN Feng;ZHANG Mei(School of Pharmacy,State Key Laboratory of Traditional Chinese Medicine Resources with Southwest Characteristics,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan Province,China;Drug Clinical Trial Institution,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610075,Sichuan Province,China)

机构地区：[1]成都中医药大学药学院西南特色中药资源国家重点实验室,四川成都611137 [2]成都中医药大学附属医院国家药物临床试验机构,四川成都610075

出　　处：《中国临床药理学杂志》2023年第13期1949-1953,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(82174273);成都中医药大学杏林学者学科人才科研提升计划基金资助项目(CXTD2018010)。

摘　　要：目的研究布洛芬注射液在中国健康受试者中单次和多次给药的药代动力学特征。方法本研究采用单中心、随机、单次和多次给药、自身交叉设计。健康受试者先后进行低(200 mg)、中(400 mg)、高(800 mg)单次给药的药代动力学研究;然后进行中剂量多次给药(每次400 mg,q6 h,连续给药至第6日晨,共计给药21次)的药代动力学研究,共计4个研究周期,每2个研究周期间给药间隔7天的清洗期。按计划的采血时间点于输液对侧的手臂采集静脉血3.5 mL,用高效液相色谱法(HPLC)测定布洛芬的血浆浓度,计算药代动力学参数。结果单次静脉输注布洛芬注射液200、400和800 mg后:C_(max)分别为(31.21±5.67)、(55.77±7.33)、(110.16±23.73)μg·mL^(-1);AUC_(0-t)分别为(73.88±13.41)、(129.16±16.37)、(239.11±42.53)μg·h·mL^(-1);AUC_(0-∞)分别为(75.54±13.38)、(131.84±17.59)、(243.33±43.41)μg·h·mL^(-1)。多次给药(q6 h,每次400 mg)达稳态后:C_(max,ss)为(62.17±8.67)μg·mL^(-1),AUC_(0-t,ss)为(146.00±24.28)μg·h·mL^(-1),AUC_(0-∞,ss)为(131.84±17.59)μg·h·mL^(-1)。多次给药后布洛芬的蓄积因子为1.34±0.37。结论单次静脉滴注后,布洛芬在200~800 mg剂量具有线性药代动力学特征;多次给药后布洛芬有一定蓄积,但一旦停止用药依然能够较快从体内消除。Objective To study the pharmacokinetic characteristics of ibuprofen injection in Chinese healthy subjects.Methods Healthy volunteers were tested by single-center,random,single and multipledose,and cross design.Subjects received single doses of intravenous ibuprofen 200,400,800 mg,respectively,and multiple doses of intravenous ibuprofen 400 mg,four times per day(every 6 h)till the morning of the sixth day in each study period.Four study cycles with 7-day washout periods between each cycle.3.5 mL of venous blood was collected.The plasma concentration of ibuprofen was determined by HPLC,and the pharmacokinetic parameters were calculated.Results After a single intravenous infusion of ibuprofen injection of 200,400 and800 mg:C_(max)were(31.21±5.67),(55.77±7.33)and(110.16±23.73)μg·mL^(-1),respectively;AUC_(0-t)were(73.88±13.41),(129.16±16.37)and(239.11±42.53)μg·h·mL^(-1),respectively;AUC_(0-∞)were(75.54±13.38),(131.84±17.59)and(243.33±43.41)μg·h·mL^(-1),respectively.After multiple doses reach steady state;C_(max,ss)was(62.17±8.67)μg·mL^(-1);AUC_(0-t,ss)was(146.00±24.28)μg·h·mL^(-1);AUC_(0-∞,ss)was(131.84±17.59)μg·h·mL^(-1).The accumulation factor of ibuprofen after multiple doses was 1.34±0.37.Conclusion After a single intravenous infusion,ibuprofen has linear pharmacokinetic characteristics in the dose range of 200-800 mg;after repeated administration,ibuprofen has a certain accumulation,but it can still be eliminated from the body quickly once the drug is stopped.

关 键 词：布洛芬 注射液 药代动力学 高效液相色谱法 

分 类 号：R971[医药卫生—药品]