| 摘要: |
| 目的:探讨环孢素(CsA)在葡聚糖硫酸钠(DSS) 诱导溃疡性结肠炎( UC) 模型大鼠体内的药物代谢动力学( 药动学) 特征。方法:将12 只SPF 级SD 大鼠按随机数表法分为UC 模型组和正常对照组各6 只,UC 模型组大鼠给予5% DSS 连续自由饮用7 d 诱导建立UC 模型,正常对照组大鼠正常饲养。第8 天分别给予两组大鼠灌胃CsA 15 mg/ kg,并于给药前和给药后不同时间点采血,测定CsA 的血药浓度,比较两组大鼠主要药动学参数。结果:与正常对照组相比,UC 模型组CsA 的体内暴露强度增加,药时曲线下面积(AUC)增加35. 69%,半衰期延长34. 94%,体内滞留时间(MRT) 延长23. 17%,体内清除率下降28. 00%(P 均<0. 05)。结论:CsA 在大鼠体内的药动学会受到UC 状态的影响而导致CsA 吸收增加,代谢减慢,CsA 体内的暴露强度增加,其具体作用机制还需要进一步研究。本研究结论可为CsA 的安全用药研究提供参考。 |
| 关键词: 环孢素 溃疡性结肠炎 药代动力学 CYP3A P 糖蛋白 |
| DOI：10.13407/j.cnki.jpp.1672-108X.2023.01.002 |
|
| 基金项目: |
|
| Pharmacokinetics of Cyclosporine in Rats with Dextran Sulfate Sodium Induced Ulcerative Colitis |
| Liu Xiongzhi1, Ye Yongfeng2 |
| (1. Children’s Hospital of Chongqing Medical University, Chongqing 400014, China; 2. The Fifth Affiliated Hospital Sun Yat-Sen University, Guangdong Zhuhai 519000, China) |
| Abstract: |
| Objective: To investigate the pharmacokinetics of cyclosporine (CsA) in rats with ulcerative colitis (UC) induced by
sodium glucan sulfate (DSS). Methods: Twelve rats were randomly divided into two groups: the control group (normal feeding) and
the UC group (5% DSS free drinking for 7 days to induce the UC model). On the 8th day, rats in both groups were given CsA 15 mg/ kg
by gavage. Blood collection was performed before and after the administration, the plasma concentration was detected and the main
pharmacokinetic parameters were compared between groups. Results: Compared with the control group, the exposure intensity of CsA in
the UC group was significantly increased, the area under the curve (AUC) was increased significantly by 35. 69%, the half-life was
extended by 34. 94%, the retention time (MRT) was also extended by 23. 17%, and the drug elimination rate was decrease significantly
by 28. 00% (P<0. 05). Conclusion: The pharmacokinetics of CsA in rats can be changed by UC disease status. Metabolism decline,
half-life extension, and increased exposure intensity, may be related to the increased CsA absorption. This study provides references for
the safe use of CsA in clinical. |
| Key words: cyclosporine ulcerative colitis pharmacokinetic CYP3A P glycoprotein |
