Relationship Between P-Glycoprotein and Second-Generation Antipsychotics

Moons, Tim; de Roo, Mariska; Claes, Stephan; Dom, Geert

doi:10.2217/pgs.11.55

Cited by 122Drug Transport and Resistance MechanismsPharmacogenetics and Drug MetabolismSchizophrenia research and treatment

Relationship Between P-Glycoprotein and Second-Generation Antipsychotics

Moons, Tim, de Roo, Mariska, Claes, Stephan, Dom, Geert·2011·Pharmacogenomics

DOI 10.2217/pgs.11.55

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Abstract

The membrane transport protein P-glycoprotein (P-gp) is an interesting candidate for individual differences in response to antipsychotics. To present an overview of the current knowledge of P-gp and its interaction with second-generation antipsychotics (SGAs), an internet search for all relevant English original research articles concerning P-gp and SGAs was conducted. Several SGAs are substrates for P-gp in therapeutic concentrations. These include amisulpride, aripiprazole, olanzapine, perospirone, risperidone and paliperidone. Clozapine and quetiapine are not likely to be substrates of P-gp. However, most antipsychotics act as inhibitors of P-gp, and can therefore influence plasma and brain concentrations of other substrates. No information was available for sertindole, ziprasidone or zotepine. Research in animal models demonstrated significant differences in antipsychotic brain concentration and behavior owing to both P-gp knockout and inhibition. Results in patients are less clear, as several external factors have to be accounted for. Patients with polymorphisms which decrease P-gp functionality tend to perform better in clinical settings. There is some variability in the findings concerning adverse effects, and no definitive conclusions can be drawn at this point.

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CYP enzymes and P-glycoprotein (P-gp) are also expressed in the intestines, which may further lower systemic concentrations.
“CYP enzymes and P-glycoprotein (P-gp) are also expressed in the intestines, which may further lower systemic concentrations [26, 27].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [26]
For orally administered drugs absorbed in the gastrointestinal tract, the drug first passes through the liver and intestines before reaching systemic circulation.
“For orally administered drugs absorbed in the gastrointestinal tract, the drug first passes through the liver and intestines before reaching systemic circulation [25–27].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [26]

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Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview
Correll, C. U., Kim, E., Sliwa, J. K., Hamm, W., Gopal, S., Mathews, M., Venkatasubramanian, R., & Saklad, S. R. (2021) · CNS Drugs · doi:10.1007/s40263-020-00779-5 · Cited by 205 · see citing works
Clinically Significant Drug Interactions with Atypical Antipsychotics
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Authors: Moons, T., de Roo, M., Claes, S., & Dom, G.
Affiliations: KU Leuven (BE)
GGz Centraal/Symfora groep, Centres for Mental Health Care, Utrechtseweg 266, 3818 EW Amersfoort, The Netherlands
Collaborative Antwerp Psychiatry Research Institute (CAPRI) & Psychiatric Centre Alexian Brothers, Boechout, Belgium
ORCID: Moons, Tim
Claes, Stephan
Dom, Geert
Venue: Pharmacogenomics
Publisher: Informa UK Limited
Published: 2011-08
Volume: 12
Issue: 8
Pages: 1193-1211
ISSN: 1462-2416 (ISSN-L)
1744-8042
DOI: 10.2217/pgs.11.55
OpenAlex: W2113251205
Cited by: 122
References: 116
Citations by year: 2026: 2 · 2025: 9 · 2024: 3 · 2023: 8 · 2022: 10 · 2021: 9 · 2020: 12 · 2019: 3 · 2018: 12 · 2017: 5 · 2016: 13 · 2015: 7 · 2014: 11 · 2013: 9 · 2012: 9
FWCI: 0.85
Type: journal article
Language: en
Open access: closed
Locations: Pharmacogenomics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords: P-glycoprotein, atypical antipsychotics, drug transporters, amisulpride, aripiprazole, olanzapine, perospirone, risperidone, paliperidone, clozapine, quetiapine, adverse drug reactions, individual differences in drug response
MeSH terms: Animals, Humans, Polymorphism, Genetic, Psychotic Disorders, Antipsychotic Agents, Treatment Outcome, Mice, Knockout, ATP Binding Cassette Transporter, Subfamily B, ATP Binding Cassette Transporter, Subfamily B, Member 1, Mice, Cytochrome P-450 CYP3A

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Relationship Between P-Glycoprotein and Second-Generation Antipsychotics

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