盐酸青藤碱脂质体缓释片人体药动学与生物等效性研究

 目的研究盐酸青藤碱脂质体缓释片人体药动学和生物等效性。方法采用随机交叉实验设计,20名健康受试者单剂量、多剂量口服受试制剂、参比制剂,采用HPLC测定血浆中盐酸青藤碱的浓度,采用3P97软件计算药动学参数。结果单剂量口服缓释片、普通片各60mg后,普通片的ρ_max(101.23±21.52)μg·L^-1明显高于缓释片的ρ_max(80.16±20.62)μg·L^-1。缓释片口服给药后的t_max为(4.35±0.81)h,较普通片t_max(2.29±0.70)h延迟,有显著差别(P<0.05),其相对生物利用度为(112.61±8.22)%。受试者多剂量口服普通片与缓释片后药动学参数稳态时曲线下面积(AUC_ss)分别为(1496.56±145.25)、(1582.61±155.82)μg·h·L^-1;ρ_max分别为(115.23±25.26)、(167.21±35.12)μg·L^-1;t_max分别为(2.35±0.72)、(4.51±0.85)h;平均稳态血药浓度(ρ_av)分别为(62.35±11.82)、(65.94±12.16)μg·L^-1;血药浓度波动度(DF)分别为(1.76±0.21)和(2.41±0.25),其相对生物利用度为(105.75±7.35)%。结论经统计学检验表明,这两种制剂的AUC_0-24h、AUC_0-∞具有生物等效性,普通片与缓释片口服时吸收程度等效,吸收速度不等效。缓释片的达峰时间明显滞后普通制剂,该缓释片显示出缓释特征。

Study on Clinical Pharmacokinetics and Bioequivalance of Sinomenine Hydrochloride Liposome Sustained-release Tablets in Healthy Volunteers

OBJECTIVE To study the clinical pharmacokinetics and bioequivalence of sinomenine hydrochloride liposome sustained-release tablets in healthy volunteers. METHODS A sensitive and rapid HPLC method was used to determine the metformin plasma concentration, single dose and multiple dose of reference and tested tablets were orally administrated to twenty male healthy volunteers in randomized crossover design. RESULTS The ρ_max(101.23±21.52)μg·L^-1 of reference tablet after single oral dose in 20 healthy volunteers was significantly higher than ρ_max(80.16±20.62)μg·L^-1 of tested tablet. The t_max(4.35±0.81)h of tested tablet was significantly longer than t_max(2.29±0.70)h of reference tablet(P<0.05).The relative bioavailability of tested tablet was found to be(112.61±8.22)%. The pharmacokinetic parameters of multiple oral doses of general tablets and sustained-release tablets were as follows: AUC_ss(1 496.56±145.25),(1 582.61±155.82)μg·h·L^-1;ρ_max(115.23±25.26),(167.21±35.12)μg·L^-1;t_max(2.35±0.72),(4.51±0.85)h;ρ_av(62.35±11.82),(65.94±12.16)μg·L^-1;DF(1.76±0.21),(2.41±0.25)respectively. The relative bioavailability of sustained release tablets to general tablets was(105.75±7.35)%. CONCLUSION Tested tablets of sinomenine hydrochloride was bioequivalent to its reference tablets. Tested tablets exhibited a sustained-release property with a significantly longer t_max and lower ρ_max.