Takano M, Hasegawa R, Fukuda T, Yumoto R, Nagai J, Murakami T
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
Eur J Pharmacol. 1998 Oct 9;358(3):289-94. doi: 10.1016/s0014-2999(98)00607-4.
The effect of cytochrome P-450 3A (CYP3A) substrates (erythromycin, midazolam) and an inhibitor (ketoconazole) on P-glycoprotein-mediated transport was studied in Caco-2, the human colon adenocarcinoma cell line expressing various functions of differentiated intestinal epithelial cells. The involvement of P-glycoprotein in the transport of these drugs was also examined. The basal-to-apical transport of rhodamine 123, a P-glycoprotein substrate, was inhibited by erythromycin, midazolam and ketoconazole, as well as by P-glycoprotein inhibitors such as verapamil. The apical-to-basal transport of rhodamine 123 was increased by these drugs. The transepithelial transport of erythromycin and midazolam, but not of ketoconazole, was much greater from the basal to apical side than from the apical to basal side. The inhibitory effect of verapamil was observed on the basal to apical transport of erythromycin, but not on midazolam and ketoconazole transport. In conclusion, erythromycin, midazolam and ketoconazole could interact with P-glycoprotein-mediated transport, and P-glycoprotein could be, at least in part, involved in the transport of erythromycin, but not of midazolam and ketoconazole, in the intestinal epithelia.
在表达分化肠上皮细胞多种功能的人结肠腺癌细胞系Caco-2中，研究了细胞色素P-450 3A（CYP3A）底物（红霉素、咪达唑仑）和一种抑制剂（酮康唑）对P-糖蛋白介导转运的影响。还检测了P-糖蛋白在这些药物转运中的作用。P-糖蛋白底物罗丹明123从基底侧向顶侧的转运受到红霉素、咪达唑仑、酮康唑以及维拉帕米等P-糖蛋白抑制剂的抑制。这些药物使罗丹明123从顶侧向基底侧的转运增加。红霉素和咪达唑仑从基底侧向顶侧的跨上皮转运比从顶侧向基底侧的跨上皮转运大得多，而酮康唑则不然。维拉帕米对红霉素从基底侧向顶侧的转运有抑制作用，但对咪达唑仑和酮康唑的转运无抑制作用。总之，红霉素、咪达唑仑和酮康唑可与P-糖蛋白介导的转运相互作用，并且P-糖蛋白至少在一定程度上参与肠道上皮中红霉素的转运，但不参与咪达唑仑和酮康唑的转运。
