Pharmacokinetics of Tacrolimus in Ulcerative Colitis Model Rats

Su Jinhe; Liu Yundi; Pan Muqian; Ye Yongfeng; Wu Heng

doi:10.13407/j.cnki.jpp.1672-108X.2022.09.002

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Pharmacokinetics of Tacrolimus in Ulcerative Colitis Model Rats

更新时间：2022-11-04

- Pharmacokinetics of Tacrolimus in Ulcerative Colitis Model Rats
- Vol. 28, Issue 9, Pages: 5-9(2022)
- 作者机构：
  
  广州中医药大学第一附属医院,广州,510405
- 作者简介：
- 基金信息：
- DOI：10.13407/j.cnki.jpp.1672-108X.2022.09.002
  CLC：
- Published：2022，
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Su Jinhe, Liu Yundi, Pan Muqian, et al. Pharmacokinetics of Tacrolimus in Ulcerative Colitis Model Rats. [J]. 28(9):5-9(2022)
DOI：

Su Jinhe, Liu Yundi, Pan Muqian, et al. Pharmacokinetics of Tacrolimus in Ulcerative Colitis Model Rats. [J]. 28(9):5-9(2022) DOI： 10.13407/j.cnki.jpp.1672-108X.2022.09.002.

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。

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.

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

Keywords

tacrolimusulcerative colitispharmacokineticsCYP3A enzymeP-glycoproteinsease status

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