Loxapine P-glycoprotein Interactions In Vitro

Andrea Reed, Keith Huie, Elke S. Perloff, James V. Cassella, Lori H. Takahashi

doi:10.2174/187231212800229255

Abstract

The antipsychotic drugs risperidone, paliperidone, olanzapine, quetiapine, aripiprazole, clozapine, haloperidol, and chlorpromazine have been reported to have various degrees of interaction (substrate or inhibitor) with the multidrug resistance transporter, P-glycoprotein (P-gp). An interaction of the antipsychotic drug loxapine with P-gp was recently reported, but an IC50 value was not determined. Loxapine (as the succinate salt) was evaluated as a P-gp substrate, and inhibitor of P-gp mediated transport of digoxin in vitro in Caco-2 cells. Loxapine was not a substrate for P-gp but did exhibit weak-to-moderate inhibition (IC50 = 9.1 μM). Since the typical steady state maximal plasma concentrations of loxapine in clinical use have been reported to be in the nanomolar range, pharmacokinetic interactions due to the inhibition of P-gp activity are not expected.

Keywords: Loxapine, P-glycoprotein, Interactions, Antipsychotic drugs, P-gp activity, BCS, ABCB1, blood-brain barrier, Psychotropic drug, In vitro