Loxapine P-glycoprotein interactions in vitro.

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

Alexza Pharmaceuticals Inc. 2091 Stierlin Ct. Mountain View, CA 94043, USA.

Drug metabolism letters 2012 Mar

filter terms:

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.

Citation

Andrea Reed, Keith Huie, Elke S Perloff, James V Cassella, Lori H Takahashi. Loxapine P-glycoprotein interactions in vitro. Drug metabolism letters. 2012 Mar;6(1):26-32