口服齐墩果酸分散片和普通片剂的人体药动学特征  

Pharmacokinetic Profiles of Oleanolic Acid Formulations in Healthy Chinese Male Volunteers

作　　者：陈瑞杰[1] 刘晓[2] 李朋梅[2] 张镭[2] 赵莉[2] 张相林[2] 

机构地区：[1]温州医学院附属二院,浙江温州325027 [2]中日友好医院临床药学室,北京100029

出　　处：《中国药学杂志》2010年第8期621-626,共6页Chinese Pharmaceutical Journal

摘　　要：目的建立HPLC-MS/MS测定人体血浆齐墩果酸(OA)浓度分析方法,探讨人体药动学特征。方法18例健康志愿者按随机分组自身交叉对照试验设计,口服OA普通片剂和分散片剂,采取受试者血样测定血药浓度,计算药动学参数,并用多元线性逐步回归分析药品暴露与各时间点血浆药物浓度的相关关系。结果根据药时数据用非房室模型进行药动学计算,得OA片和分散片的主要药动学参数:ρmax(18.9±8.0)和(17.8±7.5)μg.L-1;tmax(2.9±1.2)和(2.5±1.0)h;AUC0-48(112.2±56.6)和(109.7±41.6)μg.h.L-1;t1/2(12.3±9.0)和(16.1±12.1)h;MRT(13.6±8.6)和(18.3±11.8)h。分散片相对于普通片剂的人体生物利用度为(111.4±44.0)%。经多元线性逐步回归分析,AUC与ρ8-ρ48各呈良好相关性(r>0.7,P<0.01),并得出有限浓度值计算药品暴露量的线性回归方程式。结论OA人体药动学参数对临床用药有指导意义,有限的血样采集和浓度测定可以准确估算药品暴露程度。OBJECTIVE To establish HPLC-MS/MS method for determining oleanic acid plasma concentration and investigate oleanic acid kinetic profiles in healthy male volunteers.METHODS In a randomized,crossover and self-control study,18 male volunteers received 20 mg of OA normal tablets and dispersible tablets orally.The pharmacokinetic parameters were calculated,and the correlation between AUC and ρ was analyzed by multiple linear stepwise regression.RESULTS The concentration-time curve was described.Pharmacokinetic parameters of normal tablets and dispersible tablets were as follows： ρmax（18.9±8.0） and（17.8±7.5）μg·L^-1;tmax（2.9±1.2） and（2.5±1.0）h;AUC0-48（112.2±56.6） and（109.7±41.6）μg·h·L^-1;t1/2（12.3±9.0）and（16.1±12.1）h;MRT（13.6±8.6） and（18.3±11.8）h,respectivly.The relative bioavailability was（111.4±44.0）%.There was significant correlation between AUC and ρ8-ρ48（r 〉0.7,P〈0.01）.The linear equation for calculating drug exposure was obtained by limited sampling strategy.CONCLUSION The pharmacokinetic parameters of OA are available to clinical medicine.OA exposure could be accurate estimated by limited sampling and concentration.

关 键 词：齐墩果酸 高效液相-质谱联用法 人体药动学 

分 类 号：R969.1[医药卫生—药理学]