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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Loxapine P-glycoprotein interactions in vitro.
Andrea Reed1, Keith Huie, Elke S Perloff
1Alexza Pharmaceuticals Inc. 2091 Stierlin Ct. Mountain View, CA 94043, USA.
Drug Metabolism Letters
|February 4, 2012
Summary
Loxapine does not affect P-glycoprotein (P-gp) drug transport as a substrate. While it weakly inhibits P-gp, clinical interactions are unlikely due to low drug concentrations.
Area of Science:
- Pharmacology
- Drug Metabolism
- Biochemistry
Background:
- Several antipsychotic drugs interact with P-glycoprotein (P-gp), a key transporter in drug disposition.
- Loxapine's interaction with P-gp was previously suggested but not quantified.
Purpose of the Study:
- To evaluate loxapine as a substrate and inhibitor of P-gp.
- To determine the potential for pharmacokinetic interactions involving loxapine and P-gp.
Main Methods:
- In vitro assessment of loxapine using Caco-2 cell models.
- Determination of loxapine's P-gp substrate and inhibitor activity.
- Measurement of IC50 for P-gp inhibition.
Main Results:
- Loxapine was not identified as a substrate for P-gp.
- Loxapine demonstrated weak-to-moderate inhibition of P-gp mediated transport with an IC50 of 9.1 μM.
- The IC50 value is significantly higher than typical clinical plasma concentrations of loxapine.
Conclusions:
- Loxapine does not appear to be transported by P-gp.
- Loxapine's weak P-gp inhibitory potential is unlikely to cause significant drug-drug interactions in clinical settings.
- Further investigation into loxapine's pharmacokinetic profile is warranted.
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