pgp - publications

Predict more pgp - ligand interactions now!

1. Drug Metab Lett. 2012 Feb 2. [Epub ahead of print]

Loxapine P-glycoprotein interactions in vitro.

Reed A, Huie K, Perloff ES, Cassella JV, Takahashi LH.

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

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 ┬ÁM). 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.

PMID: 22300294 [PubMed - as supplied by publisher]