Interaction with P-glycoprotein and transport of erythromycin, midazolam and ketoconazole in Caco-2 cells.

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Takano M, Hasegawa R, Fukuda T, Yumoto R, Nagai J, Murakami T

Interaction with P-glycoprotein and transport of erythromycin, midazolam and ketoconazole in Caco-2 cells.

Eur J Pharmacol. 1998 Oct 9;358(3):289-94.

PubMed ID

9822896 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Erythromycin	P-glycoprotein 1	Protein	Humans	No	Substrate Inhibitor	Details
Ketoconazole	P-glycoprotein 1	Protein	Humans	Unknown	Inhibitor	Details