Interaction of digoxin with antihypertensive drugs via MDR1.

Article Details

Citation

Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K

Interaction of digoxin with antihypertensive drugs via MDR1.

Life Sci. 2002 Feb 15;70(13):1491-500.

PubMed ID
11895100 [ View in PubMed
]
Abstract

The multidrug transporter MDR1 (P-glycoprotein)-mediated interaction between digoxin and 29 antihypertensive drugs of various types was examined by using the MDR1 overexpressing LLC-GA5-COL150 cells, which were established by transfecting MDR1 cDNA into porcine kidney epithelial LLC-PK1 cells. These cells construct monolayers with tight junctions, and enable the evaluation of transcellular transport. The MDR1 was highly expressed on the apical membrane (urine side). The basal-to-apical and apical-to-basal transcellular transport of [3H]digoxin in LLC-GA5-COL150 cells was time- and temperature-dependent. The basal-to-apical transport of [3H]digoxin was markedly increased, whereas the apical-to-basal transport was decreased in LLC-GA5-COL150 cells, compared with the host LLC-PK1 cells, suggesting that [3H]digoxin was a substrate for MDR1. Most of the Ca2+ channel blockers used here markedly inhibited basal-to-apical transport and increased apical-to-basal transport. Exceptions were diltiazem, nifedipine and nitrendipine, which hardly showed inhibitory effects on transcellular transport of [3H]digoxin. Alpha-blocker doxazosin and beta-blocker carvedilol also inhibited transcellular transport of [3H]digoxin, but none of the angiotensin converting enzyme inhibitors and AT1 angiotensin II receptor antagonists used here were active. These observations will promote understanding of the digoxin-drug interactions resulting from their actions on MDR1, and which may aid in avoiding these unexpected effects of digoxin.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
CandesartanP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
Candesartan cilexetilP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
CaptoprilP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
CarvedilolP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
CilazaprilP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
DoxazosinP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
EnalaprilP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
LosartanP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Details