候选药物HY152-J大鼠在体肠吸收动力学研究  

Intestinal absorption kinetics of candidate drug HY152-J in rats in vivo

作　　者：李梁[1] 顾留歌 檀琼[1] 肖峰[1] 许玲美[1] 秦燕[1] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点实验室/上海市生物物质成药性评价专业技术服务平台,上海200437

出　　处：《中国新药杂志》2017年第6期665-669,共5页Chinese Journal of New Drugs

基　　金：上海市科委"科技创新行动计划"生物医药领域科技支撑项目(13431900203)

摘　　要：目的:研究候选药物HY152-J在大鼠不同肠段的吸收动力学特性。方法:采用大鼠在体单向肠灌流模型考察HY152-J在大鼠不同肠段的吸收动力学特性;利用HPLC法测定肠灌流液中HY152-J含量;考察不同肠段、不同质量浓度、不同p H介质以及P-糖蛋白(P-gp)抑制剂4个因素对HY152-J肠吸收的影响。结果:HY152-J在大鼠十二指肠、空肠、回肠和结肠的吸收速率常数(Ka)和表观渗透系数(Papp)无显著性差异(P>0.05);与低浓度(25μg·m L^(-1))组相比,高浓度(100μg·m L^(-1))组中HY152-J的Ka和Papp均存在非常显著性差异(P<0.01),中浓度(50μg·m L^(-1))组中HY152-J的Papp有显著性差异(P<0.05);不同p H的介质对Ka和Papp均无显著性影响(P>0.05);P-gp抑制剂对HY152-J的肠吸收没有显著性影响(P>0.05)。结论:HY152-J在不同肠段均有吸收,且无明显的特定吸收部位;在25~100μg·m L^(-1)范围内,随浓度增大,其吸收有逐渐饱和趋势,初步推断HY152-J的吸收机制为主动转运;HY152-J可能不是P-gp的底物。Objective： To study the in situ intestinal absorption characteristics of candidate drug HY152-J in a rat model. Methods： In situ single-pass intestine perfusion model was adopted to study the absorption behaviors of HY152-J in different intestine segments. The concentrations of HY152-J in the perfusate were determined by HPLC. And we investigated the influences of intestine segments,drug concentrations,p H values of perfusate,and P-glycoprotein inhibitor on intestinal absorption of HY152-J. Results： The absorption rate constants（ Ka） and apparent permeability coefficients（ Papp） of HY152-J in the duodenum,jejunum,ileum and colon of rats had no obvious difference（ P 〉 0. 05）. Compared with the group of low concentration（ 25 μg·m L-1）,the Kaand Pappvalues of HY152-J had conspicuous difference in high concentration（ 100 μg·m L-1） group（ P 〈 0. 01） and the Pappvalues of HY152-J had apparent difference in moderate concentration（ 50 μg·m L-1） group（ P 〈 0. 05）.Different p H values of perfusate had no significant effect on the Kaand Pappvalues of HY152-J（ P 〉 0. 05）. And the P-gp inhibitor had little influence on the intestinal absorption of HY152-J（ P 〉 0. 05）. Conclusion： HY152-J can be absorbed in the whole segments of the intestine in rats,and dose not have a special absorption region. The absorption of HY152-J does not show an increase with concentrations in the range of 25 ~ 100 μg·m L-1. It preliminarily suggests that the absorption of HY152-J complies with active absorption. In addition,HY152-J mightnot be a substrate of P-gp.

关 键 词：HY152-J 在体单向肠灌流模型 高效液相色谱 重量法 肠吸收 

分 类 号：R96[医药卫生—药理学]