美沙拉嗪肠溶缓释颗粒剂的大鼠药动学及胃肠道分布研究

目的 评价新型制剂美沙拉嗪肠溶缓释颗粒剂在SD大鼠体内的药动学以及在胃肠道的分布情况，了解该制剂临床前药动学特征及胃肠道分布特征。方法 采用大鼠口服给药，测定其血药浓度和胃肠道残留浓度；以美沙拉嗪缓释颗粒剂（市售制剂）为参照，评价美沙拉嗪肠溶缓释颗粒剂（自研制剂）在大鼠体内吸收和消除过程、相对生物利用度、药物在胃肠道分布情况。结果 美沙拉嗪肠溶缓释颗粒剂在大鼠体内，与美沙拉嗪缓释颗粒剂以美沙拉嗪表征的相对生物利用度为(90.62±9.36)%。美沙拉嗪肠溶缓释颗粒剂口服给药后在2~8 h时间段，药物在胃部存在高浓度分布，随着时间的推移逐步进入并残存于空肠、回肠和结肠，6~12 h后在结肠达到高浓度分布，其结果有助于美沙拉嗪药物的体内吸收，以及缓释颗粒剂在作用部位的定点释放与发挥疗效。结论 美沙拉嗪肠溶缓释颗粒剂吸收和消除过程基本呈线性动力学特征，药动学参数与市售制剂无显著性差异，且在胃肠道有一定流动性，包衣对消化液耐受性好，胃肠道分布特征有利于药物的体内吸收和作用部位的定点释放。

Study on pharmacokinetic and gastrointestinal distribution study of mesalazine enteric-coated sustained-release granules in rats

Objective To evaluate the pharmacokinetics of the new mesalazine enteric-coated sustained-release granules in SD rats and their distribution in the gastrointestinal tract, and to understand the preclinical pharmacokinetics and gastrointestinal distribution characteristics of the preparation.Methods Rats were administered orally to determine the drug concentrations in plasma samples and in the gastrointestinal tract. The commercially available mesalazine sustained-release granule was used as a reference to self-developed one to evaluate the process of absorption and elimination in vivo, relative bioavailability, and distribution in the gastrointestinal tract.Results The relative bioavailability of mesalazine enteric-coated sustained-release granule and non-enteric-coated one characterized by mesalazine was 89.62% ± 9.36%. After oral administration of mesalazine enteric-coated sustained-release granules, the drug has a high concentration distribution in the stomach within 2-8 hours, and gradually enters and remains in the jejunum, ileum and colon over time for 6-12 hours and then reaching a high concentration distribution in the colon. This help for the absorption of mesalazine, as well as the fixed-point release of the drug to produce a therapeutic effect.Conclusion The absorption and elimination process of mesalazine enteric sustained-release granule showed linear kinetic characteristics. There was no significant difference in pharmacokinetic parameters from the commercially available formulations, and it had a certain fluidity in the gastrointestinal tract. Good gastrointestinal distribution characteristics help the absorption of drugs in the body and the targeted release of the site of action