Evidence map›Paper›PMID 28160505›Full record

ArticleBritish journal of clinical pharmacology2017

Cytochrome P450-mediated interaction between perazine and risperidone: implications for antipsychotic polypharmacy.

Michael Paulzen, Ekkehard Haen, Christoph Hiemke, Benedikt Stegmann, Sarah E Lammertz, Gerhard Gründer, Georgios Schoretsanitis

Open access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.8field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Michael PaulzenDepartment of Psychiatry, Psychotherapy and Psychosomatics, and JARA - Translational Brain Medicine, RWTH Aachen University, Aachen, Germany.ORCID 0000-0003-4198-5160
Ekkehard HaenClinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
Christoph HiemkeDepartment of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Mainz, Germany.
Benedikt StegmannClinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
Sarah E LammertzDepartment of Psychiatry, Psychotherapy and Psychosomatics, and JARA - Translational Brain Medicine, RWTH Aachen University, Aachen, Germany.
Gerhard GründerDepartment of Psychiatry, Psychotherapy and Psychosomatics, and JARA - Translational Brain Medicine, RWTH Aachen University, Aachen, Germany.
Georgios SchoretsanitisDepartment of Psychiatry, Psychotherapy and Psychosomatics, and JARA - Translational Brain Medicine, RWTH Aachen University, Aachen, Germany.ORCID 0000-0002-3851-4117
Jülich Aachen Research Alliance · DEUniversity of Regensburg · DEJohannes Gutenberg University Mainz · DEUniversity Hospital of Bern · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlthough clinically widespread, scientific evidence for antipsychotic polypharmacy is still limited. Combining different drugs increases the potential for drug-drug interactions, enhancing the risk of adverse drug reactions. We aimed to unravel the potential pharmacokinetic interactions between risperidone (RIS) and perazine.

methodsUsing a therapeutic drug monitoring database containing plasma concentrations of RIS and its active metabolite [9-hydroxyrisperidone (9-OH-RIS)], we considered two groups: a group of patients under antipsychotic monotherapy with RIS (n = 40) and a group of patients that was comedicated with perazine (n = 16). Groups were matched for demographic characteristics and daily dosage of RIS. Plasma concentrations, concentrations corrected for the dose (C/D) of RIS, 9-OH-RIS and the active moiety (RIS + 9-OH-RIS), as well as the metabolic ratios of concentrations of 9-OH-RIS/RIS, were compared using nonparametric tests.

resultsAll parameters other than plasma concentrations and the C/D ratio of 9-OH-RIS differed between groups. Median values for plasma concentrations of the active moiety and C/D of the active moiety were higher in the perazine group (P < 0.001 and P < 0.001, respectively). Differences were driven by variations in the plasma concentrations and C/D of RIS, which were higher in the perazine group (P < 0.001 and P < 0.001, respectively). Metabolic ratios were lower in the perazine group (P = 0.003). DISCUSSION: The coadministration of perazine in RIS-medicated patients leads to significantly higher plasma concentrations and C/D values of RIS and its active moiety, and a lower metabolic ratio, reflecting the cytochrome P450 (CYP) 2D6 phenotype. We suggest that the mechanism underlying the effect of perazine on RIS metabolism is based on an inhibition of CYP2D6 and CYP3A4 activity.

Indexed as

PolypharmacyAdultAntipsychotic AgentsCytochrome P-450 CYP2D6Cytochrome P-450 CYP2D6 InhibitorsCytochrome P-450 CYP3ACytochrome P-450 CYP3A InhibitorsDrug InteractionsDrug MonitoringFemaleHumansMaleMental DisordersMiddle AgedPaliperidone PalmitatePerazineAntipsychotic AgentsCytochrome P-450 CYP2D6Cytochrome P-450 CYP2D6 InhibitorsCytochrome P-450 CYP3ACytochrome P-450 CYP3A InhibitorsPaliperidone PalmitatePerazineRisperidoneantipsychotic polypharmacyCYP2D6CYP3A4cytochrome P450interactionperazinepharmacokineticsrisperidonetherapeutic drug monitoring

Identifiers

PMID28160505
PMCPMC5510064
OpenAlexW2585125306

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.