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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.
khuie@alexza.com.

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]