盐酸异丙嗪在大鼠单向肠灌流模型吸收特性

Intestinal Absorption Characteristics of Promethazine Hydrochloride in Rat Single-pass Intestinal Perfusion Model

目的研究盐酸异丙嗪在大鼠肠道不同部位的吸收特性,为新的制剂研发提供依据。方法建立大鼠在体单向肠灌流模型,采用高效液相色谱(HPLC)法测定25,50,100μg·mL^(-1)盐酸异丙嗪在肠道不同部位浓度变化,计算吸收速率常数(Ka)和表观吸收系数(P_(app))。结果十二指肠段和回肠段随着盐酸异丙嗪浓度增加,同一肠段的Ka和P_(app)都显著增加;在盐酸异丙嗪50μg·mL^(-1)时空肠段Ka为(28.00±0.02)×10^(-2)min^(-1)和P_(app)为(9.64±0.22),均为最大,结肠段随着浓度增加,Ka和P_(app)没有显著变化。结论异丙嗪在各个肠段都有吸收,十二指肠和回肠段较为明显,其他肠段则较低,吸收大小依次是十二指肠>回肠>空肠>结肠,盐酸异丙嗪在小肠段吸收较好,符合肠道吸收特性。

Objective To study the absorption characteristics of promethazine hydrochloride in different parts of rat intestine, provide evidence for the development of new preparation. Methods Rat single-pass intestinal perfusion model was established. By using high performance liquid chromatography （HPLC）, 25, 50, 100 μg·mL^-1 promethazine hydrochloride concentration changing in different parts of the intestine was detected. Through the relevant calculation, the absorption rate constant （ Ka ） , and the apparent absorption coefficient （ Papp ） were obtained. Results With the concentration increase of promethazine hydrochloride in duodenal and ileal segments, the Ka and Papp increased significantly in the same part. Ka was （28.00±0.02）×10^-2min^-1 and Papp was （9.64±0.22） in the jejunum were the highest when the promethazine hydrochloride concentration was 50 μg·mL^-1 . As the concentration increased in colon, there were no significant changes in Ka and Papp . Conclusion Promethazine hydrochloride is absorbed in various intestinal segments, most obviously in duodenum and ileum, the absorption order is duodenum〉ileum〉jejunum＆gt;colon. Promethazine hydrochloride is absorbed most in the small intestine, in line with the intestinal absorption characteristics.