| 引用本文: | 温金华,孙文雄,程晓华,曹端文,余路易,李蒲.克拉霉素对Caco-2细胞转运他克莫司的影响及机制研究[J].中国现代应用药学,2022,39(3):329-333. |
| WEN Jinhua,SUN Wenxiong,CHENG Xiaohua,CAO Duanwen,YU Luyi,LI Pu.Effect of Clarithromycin on Tacrolimus Transport in Caco-2 Cells and Its Mechanism[J].Chin J Mod Appl Pharm(中国现代应用药学),2022,39(3):329-333. |
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| 摘要: |
| 目的 探讨克拉霉素对Caco-2细胞转运他克莫司的影响及机制。方法 用化学发光免疫分析法测定他克莫司药物浓度；建立Caco-2细胞单层模型，计算表观渗透系数，比较不同浓度他克莫司在Caco-2细胞单层中转运及不同浓度克拉霉素抑制他克莫司的转运。结果 他克莫司浓度为20，40和80 μg·mL-1时吸收渗透系数PappAP-BL分别为（2.47±0.09）×10-6，（3.91±0.17）×10-6和（4.49±0.16）×10-6 cm·s-1；分泌渗透系数PappBL-AP分别为（6.05±0.21）×10-6，（9.86±0.70）×10-6和（11.75±0.28）×10-6 cm·s-1；外流比（apparent permeability ratio，PDR）分别为2.45±0.03，2.52±0.12和2.62±0.11；加入不同浓度的克拉霉素（15，30，60 μg·mL-1）后，分泌渗透系数显著降低，而吸收系数影响不大，PDR随着克拉霉素浓度增加显著降低。结论 Caco-2细胞外排转运体可能参与了他克莫司的转运，克拉霉素合用他克莫司可显著影响他克莫司的吸收。 |
| 关键词: 他克莫司 克拉霉素 Caco-2细胞 转运 |
| DOI：10.13748/j.cnki.issn1007-7693.2022.03.007 |
| 分类号:R965.1 |
| 基金项目:江西省杰出青年人才资助计划（20192BCBL23018） |
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| Effect of Clarithromycin on Tacrolimus Transport in Caco-2 Cells and Its Mechanism |
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WEN Jinhua, SUN Wenxiong, CHENG Xiaohua, CAO Duanwen, YU Luyi, LI Pu
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Department of GCP, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
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| Abstract: |
| OBJECTIVE To explore the effect and the mechanism of clarithromycin on the transport of tacrolimus in Caco-2 cells. METHODS The concentration of tacrolimus was determined by chemiluminescence immunoassay. The single layer model of Caco-2 cells was established, the apparent permeability coefficient was calculated, and to compare the transport of tacrolimus in Caco-2 cell monolayer at different concentrations and the inhibition of tacrolimus transport by clarithromycin at different concentrations. RESULTS When tacrolimus concentration was 20, 40 and 80 μg·mL-1, the absorption coefficient PappAP-BL was (2.47±0.09)×10-6, (3.91±0.17)×10-6 and (4.49±0.16)×10-6cm·s-1, respectively, and the secretory coefficient PappBL-AP was (6.05±0.21)×10-6, (9.86±0.70)×10-6and (11.75±0.28)×10-6cm·s-1 respectively; the apparent permeability ratio(PDR) was 2.45±0.03, 2.52±0.12 and 2.62±0.11 respectively. After adding different concentrations of clarithromycin(15, 30, 60 μg·mL-1), the secretory permeability coefficient decreased significantly, but the absorption coefficient was not affected, and the PDR decreased significantly with the increase of clarithromycin concentration. CONCLUSION The extracellular transporters of Caco-2 may be involved in the transport of tacrolimus and the absorption tacrolimus could be apparently affected by combination of clarithromycin. |
| Key words: tacrolimus clarithromycin Caco-2 cells transport |
