Inhibition of P-glycoprotein by newer antidepressants.
Article Details
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Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE
Inhibition of P-glycoprotein by newer antidepressants.
J Pharmacol Exp Ther. 2003 Apr;305(1):197-204.
- PubMed ID
- 12649369 [ View in PubMed]
- Abstract
Pharmacokinetic drug-drug interactions often occur at the level of P-glycoprotein (Pgp). To study possible interactions caused by the newer antidepressants we investigated citalopram, fluoxetine, fluvoxamine, paroxetine, reboxetine, sertraline, and venlafaxine and their major metabolites desmethylcitalopram, norfluoxetine, paroxetine-metabolite (paroxetine-M), desmethylsertraline, N-desmethylvenlafaxine, and O-desmethylvenlafaxine for their ability to inhibit Pgp. Pgp inhibition was studied by a fluorometric assay using calcein-acetoxymethylester as Pgp substrate and two different cell systems: L-MDR1 cells (model for human Pgp) and primary porcine brain capillary endothelial cells (pBCECs, model for the blood-brain barrier). Both cell systems proved to be suitable for the evaluation of Pgp inhibitory potency of drugs. All antidepressants tested except O-desmethylvenlafaxine showed Pgp inhibitory activity with sertraline, desmethylsertraline, and paroxetine being the most potent, comparable with the well known Pgp inhibitor quinidine. In L-MDR1 cells fluoxetine, norfluoxetine, fluvoxamine, reboxetine, and paroxetine-M revealed intermediate Pgp inhibition and citalopram, desmethylcitalopram, venlafaxine, and N-desmethylvenlafaxine were only weak inhibitors. The ranking order was similar in pBCECs. The fact that some of the compounds tested exert Pgp inhibitor effects at similar concentrations as quinidine suggests that pharmacokinetic drug-drug interactions between the newer antidepressants and Pgp substrates should now be thoroughly studied in vivo.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Citalopram P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Fluoxetine P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Fluvoxamine P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Paroxetine P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Quinidine P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Reboxetine P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Sertraline P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Venlafaxine P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareVenlafaxinePropafenone The serum concentration of Venlafaxine can be increased when it is combined with Propafenone.