| 摘要: |
| 目的：考察他克莫司（FK506）在葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎（UC）模型大鼠体内的药代动力学特点。方法：将12只大鼠随机分为UC组和正常组各6只，UC组给予5% DSS连续自由饮用7 d诱导建立UC模型，第8天分别给予两组大鼠灌胃FK506 1 mg/kg，于给药前和给药后不同时间点采血，测定FK506血药浓度，比较分析两组主要药动学参数。结果：与正常组相比，UC组体内的FK506暴露强度增加，AUC0-t增加了44.06%，半衰期延长了1.85 h（近50%），体内滞留时间（MRT0-∞）延长了37.0%，清除率下降了32.25%（P均<0.05）。结论：FK506在大鼠体内的药动学会受到UC状态的影响，导致FK506代谢下降，半衰期延长，暴露强度增加，可能与UC状态影响P糖蛋白和CYP3A酶活性有关。 |
| 关键词: 他克莫司 溃疡性结肠炎 药代动力学 CYP3A酶 P糖蛋白 疾病状态 |
| DOI：doi:10.13407/j.cnki.jpp.1672-108X.2022.09.002 |
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| 基金项目: |
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| Pharmacokinetics of Tacrolimus in Ulcerative Colitis Model Rats |
| Su Jinhe1, Liu Yundi1, Pan Muqian2, Ye Yongfeng3, Wu Heng1 |
| (1. The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; 2. Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China; 3. The Fifth Affiliated Hospital, Sun Yat-Sen University, Guangdong Zhuhai 519000, China) |
| Abstract: |
| Objective: To probe into the pharmacokinetic characteristics of tacrolimus (FK506) in dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in rats. Methods: Twelve rats were randomly divided into the UC group and the normal group, with 6 cases in each group. The UC group was given 5% DSS for 7 d to induce the UC model. On the 8th d, two groups were given FK506 for 1 mg/kg by gavage. Blood samples were collected at different time points before and after administration to determine the concentration of FK506, and the main pharmacokinetic parameters of two groups were compared and analyzed. Results: Compared with the normal group, the exposure intensity of FK506 in the UC group increased, the AUC0-t increased by 44.06%, the half-life was prolonged by 1.85 h (nearly 50%), the in vivo retention time (MRT0-∞) was prolonged by 37.0% and the drug clearance rate increased by 37.0% (P<0.05). Conclusion: The pharmacokinetics of FK506 in rats is affected by UC status, resulting in decreased FK506 metabolism, prolonged half-life, and increased exposure intensity, which may be related to the effect of UC status on P-glycoprotein and CYP3A enzyme activities. |
| Key words: tacrolimus ulcerative colitis pharmacokinetics CYP3A enzyme P-glycoprotein disease status |
