Gastrointestinal absorption of pimozide is enhanced by inhibition of P-glycoprotein

摘要: Drug-drug interaction was suggested to have played a role in the recent death due cardiac arrest of patient taking pimozide, sertraline and aripiprazole antipsychotic/antidepressant combination therapy. Here, we investigated possible involvement P-glycoprotein (P-gp)-mediated among these drugs, using vitro methods. ATPase assay confirmed that pimozide is P-gp substrate, might act as inhibitor at higher concentrations. The maximum transport rate (Jmax) half-saturation concentration (Kt) for carrier-mediated estimated by means efflux P-gp-overexpressing LLC-GA5-CoL150 cells were 84.9 ± 8.9 pmol/min/mg protein, 10.6 4.7 μM, respectively. These results indicate good it appears potential cause drug-drug interactions digestive tract clinically relevant gastrointestinal Moreover, or significantly decreased ratio cells. Transport studies Caco-2 cell monolayers consistent with cells, P-gp-mediated may occur tract. Thus, inhibition and/or increase permeability co-administered resulting an increased blood which known be associated risk QT prolongation, life-threatening side effect.