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80μg·mL^(-1)时吸收渗透系数P_(appAP-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P_(appBL-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(15,30,60μg·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。
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 80μg·mL^(-1),the absorption coefficient P_(appAP-BL)was(2.47±0.09)×10^(-6),(3.91±0.17)×10^(-6)and(4.49±0.16)×10^(-6)cm·s^(-1),respectively,and the secretory coefficient P_(appBL-AP)was(6.05±0.21)×10^(-6),(9.86±0.70)×10^(-6)and(11.75±0.28)×10^(-6)cm·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(15,30,60μg·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.
作者
温金华
孙文雄
程晓华
曹端文
余路易
李蒲
WEN Jinhua;SUN Wenxiong;CHENG Xiaohua;CAO Duanwen;YU Luyi;LI Pu(Department of GCP,The First Affiliated Hospital of Nanchang University,Nanchang 330006,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2022年第3期329-333,共5页
Chinese Journal of Modern Applied Pharmacy
基金
江西省杰出青年人才资助计划(20192BCBL23018)
作者简介
温金华,男,博士,硕导,E-mail:wenjh8606@163.com
