布洛芬缓释胶囊单剂量与多剂量给药的人体药动学及生物等效性研究

目的：建立高效液相色谱法测定人血浆中布洛芬浓度,并应用于两种布洛芬缓释制剂的人体生物等效性研究。方法：采用双周期自身随机交叉试验设计,24名男性健康志愿者分别单剂量、多剂量口服布洛芬缓释胶囊受试制剂和参比制剂300mg,采用高效液相色谱法测定人血浆中布洛芬浓度,利用DAS 2.0程序计算主要药动学参数,并对两种制剂进行生物等效性评价。结果：单剂量口服受试制剂和参比制剂后血浆中布洛芬的Cmax分别为（12.7±5.4）和（13.5±5.9）μg/mL,tmax分别为（5.5±1.4）和（5.1±1.0）h,AUC0→24分别为（96.8±50.2）和（95.7±45.4）μg·h·mL^-1。多剂量口服受试制剂和参比制剂后血浆中布洛芬的Cmax分别为（14.1±5.3）和（14.9±6.4）μg/mL,tmax分别为（4.8±1.0）和（4.6±0.9）h,Cav分别为（8.3±3.4）和（8.6±4.3）μg/mL,DF值分别为（117.2±35.3）%和（131.7±35.1）%。经统计学检验,两种制剂主要药动学参数间无统计学差异（P〉0.05）。结论：所建立的高效液相色谱法适合用于人体血浆中布洛芬测定。布洛芬受试制剂和参比制剂具有生物等效性。

Study of pharmacokinetics and relative bioequivalence of single and multiple oral doses of ibuprofen sustained-release capsules

AIM：To develop a high performance liquid chromatography method for the determination of ibuprofen in human plasma,and to evaluate the bioequivalence of two preparations of ibuprofen.METHODS：Twenty-four healthy male volunteers were given a single or multiple oral dose of 300 mg sustained-release capsule of each preparation in a randomized twoway,crossover study.Serial plasma samples were analyzed by a high performance liquid chromatography method.Pharmacokinetic parameters were calculated and compared statistically to evaluate the bioequivalence between the two preparations by DAS 2.0program.RESULTS：After orally a single dose（300mg）,the major pharmacokinetic parameters of the test and reference preparations were as follows：Cmaxwere（12.7± 5.4）and（13.5±5.9）μg/mL,tmaxwere（5.5± 1.4）and（5.1±1.0）h,AUC0→24were（96.8± 50.2）and（95.7±45.4）μg·h·mL^-1.After orally a multiple dose（300mg）,the major pharmacokinetic parameters of the test and reference preparations were as follows：tmaxwere（4.8± 1.0）and（4.6±0.9）h,Cmaxwere（14.1±5.3） and（14.9±6.4）μg/mL,Cavwere（8.3±3.4） and（8.6±4.3）μg/mL,and DF were（117.2± 35.3）%and（131.7±35.1）%.Main pharmacokinetic parameters between the two formulations in both single and multiples dose studies showed no statistical difference（P〉0.05）.CONCLUSION：The method was proved to be suitable for the determination of ibuprofen in human plasma.The result of the statistical analysis showed that two formulations of ibuprofen were bioequivalent.