盐酸氯卡色林饱和溶解度、油水分配系数的测定及大鼠在体肠吸收  

Saturation solubility of lorcaserin hydrochloride and its apparent oil-water partition coefficient and in situ intestinal absorption in rats

作　　者：王重阳 蒋成君 王梦文 陶福林 朱文涛 汪电雷 WANG Chongyang;JIANG Chengjun;WANG Mengwen;TAO Fulin;ZHU Wentao;WANG Dianlei(College of Pharmacy,Anhui University of Chinese Medicine,Hefei 230011,China)

机构地区：[1]安徽中医药大学药学院,安徽合肥230011

出　　处：《皖南医学院学报》2022年第4期321-325,共5页Journal of Wannan Medical College

基　　金：安徽高校自然科学研究项目(KJ2019ZD33)。

摘　　要：目的:测定盐酸氯卡色林的饱和溶解度和表观油水分配系数及其在大鼠肠道的吸收动力学特征。方法:采用高效液相色谱法测定37℃下盐酸氯卡色林在不同pH缓冲液的饱和溶解度及表观油水分配系数,大鼠在体单向肠灌流实验,按重量法计算动力学参数。结果:盐酸氯卡色林在不同pH缓冲溶液的饱和溶解度均>400 mg/mL;在正辛醇-水体系下,盐酸氯卡色林的表观油水分配系数为2.464(lg P=2.464);盐酸氯卡色林在全肠段均有吸收,与其在十二指肠的吸收速率常数(K_(a))、表观吸收系数(P_(app))相比,空肠、回肠和结肠的K_(a)和P_(app)差异均有统计学意义(P<0.05),且不同浓度(1、6、24μg/mL)的盐酸氯卡色林的K_(a)及P_(app)差异无统计学意义(P>0.05)。结论:盐酸氯卡色林属于高溶解性药物,且其表观油水分配系数受溶液pH影响不大;在大鼠全肠段均有吸收,以十二指肠的吸收最好,其药物吸收机制可能为被动扩散。Objective:To determine the saturation solubility and apparent oil-water partition coefficient of lorcaserin hydrochloride,and observe the absorption kinetics of lorcaserin hydrochloride in the intestinal tract of rats.Methods:High performance liquid chromatography(HPLC)was performed to determine the saturation solubility and apparent oil-water partition coefficient in different pH buffer solution.Then in situ rat intestinal perfusion model was used to calculate the kinetic parameters by weight methods.Results:The saturation solubility of lorcaserin hydrochloride in different pH buffer solution was more than 400 mg/mL.The apparent oil-water partition coefficient of lorcaserin hydrochloride was 2.464(lg P=2.464).Lorcaserin hydrochloride was generally absorbed in the whole intestine of rats.The absorption rate constant(K_(a))and the apparent absorption coefficient(P_(app))were significantly different in jejunum,ileum and colon compared to duodenum(P<0.05),yet there were no significant differences in K_(a) and P_(app) of lorcaserin hydrochloride among different concentrations(1,6,24μg/mL)(P>0.05).Conclusion:Lorcaserin hydrochloride representing a highly soluble drug is less likely affected with its apparent oil-water distribution coefficient by pH value of solution,and can be absorbed in the whole intestine of rats,with optimal absorption in the duodenum.The potential mechanism of such absorption may be associated with passive diffusion of lorcaserin hydrochloride in situ.

关 键 词：盐酸氯卡色林 饱和溶解度 表观油水分配系数 肠吸收 

分 类 号：R914.5[医药卫生—药物化学] R-332[医药卫生—药学]