Pharmacokinetics of risperidone in different application forms – Comparing long-acting injectable and oral formulations

Georgios Schoretsanitis; Jose de Leon; Ekkehard Haen; Benedikt Stegmann; Christoph Hiemke; Gerhard Gründer; Michael Paulzen

doi:10.1016/j.euroneuro.2017.11.009

Pharmacokinetics of risperidone in different application forms – Comparing long-acting injectable and oral formulations

Georgios Schoretsanitis, Jose de Leon, Ekkehard Haen, Benedikt Stegmann, Christoph Hiemke, Gerhard Gründer, Michael Paulzen

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20 Scopus citations

Abstract

We aimed to explore the differences in the pharmacokinetics of risperidone between oral and long-acting injectable (LAI) formulations using a large database of therapeutic drug monitoring (TDM). Plasma concentrations of risperidone (RIS), its active metabolite (9-OH-RIS) and the active moiety (AM) (RIS+9-OH-RIS), their concentration-to-dose (C/D) ratios and ratio of RIS/9-OH-RIS (an index of CYP2D6 metabolic activity) were used to compare patients receiving risperidone orally (n = 851) and those treated with LAI RIS (n = 63). Patients taking CYP inducers or inhibitors or with liver/renal impairment were eliminated. Our study demonstrated that patients on LAI RIS, despite slightly higher RIS doses in the oral group, showed no significant differences in total AM or 9-OH-RIS. Conversely, RIS concentration, RIS C/D ratio and total C/D ratio were slightly higher in the LAI RIS group, reaching significance due to the large sample size. More importantly, the median ratio of RIS/9-OH-RIS was 0.52 in LAI RIS vs. 0.25 in the oral group, providing a significant difference (p < 0.001). After controlling for confounding factors, we replicated the RIS/9-OH–RIS ratio increases in patients with LAI RIS, probably reflecting a decrease in first-pass metabolism. More studies are required to establish the clinical use of TDM for patients on LAI RIS.

Original language	English
Pages (from-to)	130-137
Number of pages	8
Journal	European Neuropsychopharmacology
Volume	28
Issue number	1
DOIs	https://doi.org/10.1016/j.euroneuro.2017.11.009
State	Published - Jan 2018

Bibliographical note

Funding Information:
Dr. Haen received speaker’s or consultancy fees from the following pharmaceutical companies: Servier, Novartis, and Janssen-Cilag. He is managing director of AGATE, a non-profit working group to improve drug safety and efficacy in the treatment of psychiatric diseases. Dr. Gründer has served as a consultant for Boehringer Ingelheim (Ingelheim, Germany), Cheplapharm (Greifswald, Germany), Eli Lilly (Indianapolis, IN, USA), Lundbeck (Copenhagen, Denmark), Ono Pharmaceuticals (Osaka, Japan), Roche (Basel, Switzerland), Servier (Paris, France), and Takeda (Osaka, Japan). He has served on the speakers’ bureau of Eli Lilly, Gedeon Richter (Budapest, Hungary), Janssen Cilag (Neuss, Germany), Lundbeck, Roche, Servier, and Trommsdorf (Aachen, Germany). He has received grant support from Boehringer Ingelheim and Roche. He is co-founder of Pharma Image GmbH (Düsseldorf, Germany) and Brainfoods UG (Selfkant, Germany). Dr. Hiemke has received speaker’s or consultancy fees from the following pharmaceutical companies: Janssen, Lilly and Servier. He is managing director of the psiac GmbH which provides an internet-based drug-drug interaction program for psychopharmacotherapy. Drs. Schoretsanitis, de Leon, Stegmann and Paulzen had no conflicts of interest during the last 12 months.

Publisher Copyright:
© 2017 Elsevier B.V. and ECNP

Keywords

cytochrome P-450 CYP2D6
drug monitoring
risperidone/administration and dosage
risperidone/metabolism
risperidone/pharmacokinetics

ASJC Scopus subject areas

Pharmacology
Neurology
Clinical Neurology
Psychiatry and Mental health
Biological Psychiatry
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.euroneuro.2017.11.009

Cite this

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title = "Pharmacokinetics of risperidone in different application forms – Comparing long-acting injectable and oral formulations",

abstract = "We aimed to explore the differences in the pharmacokinetics of risperidone between oral and long-acting injectable (LAI) formulations using a large database of therapeutic drug monitoring (TDM). Plasma concentrations of risperidone (RIS), its active metabolite (9-OH-RIS) and the active moiety (AM) (RIS+9-OH-RIS), their concentration-to-dose (C/D) ratios and ratio of RIS/9-OH-RIS (an index of CYP2D6 metabolic activity) were used to compare patients receiving risperidone orally (n = 851) and those treated with LAI RIS (n = 63). Patients taking CYP inducers or inhibitors or with liver/renal impairment were eliminated. Our study demonstrated that patients on LAI RIS, despite slightly higher RIS doses in the oral group, showed no significant differences in total AM or 9-OH-RIS. Conversely, RIS concentration, RIS C/D ratio and total C/D ratio were slightly higher in the LAI RIS group, reaching significance due to the large sample size. More importantly, the median ratio of RIS/9-OH-RIS was 0.52 in LAI RIS vs. 0.25 in the oral group, providing a significant difference (p < 0.001). After controlling for confounding factors, we replicated the RIS/9-OH–RIS ratio increases in patients with LAI RIS, probably reflecting a decrease in first-pass metabolism. More studies are required to establish the clinical use of TDM for patients on LAI RIS.",

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author = "Georgios Schoretsanitis and {de Leon}, Jose and Ekkehard Haen and Benedikt Stegmann and Christoph Hiemke and Gerhard Gr{\"u}nder and Michael Paulzen",

note = "Funding Information: Dr. Haen received speaker{\textquoteright}s or consultancy fees from the following pharmaceutical companies: Servier, Novartis, and Janssen-Cilag. He is managing director of AGATE, a non-profit working group to improve drug safety and efficacy in the treatment of psychiatric diseases. Dr. Gr{\"u}nder has served as a consultant for Boehringer Ingelheim (Ingelheim, Germany), Cheplapharm (Greifswald, Germany), Eli Lilly (Indianapolis, IN, USA), Lundbeck (Copenhagen, Denmark), Ono Pharmaceuticals (Osaka, Japan), Roche (Basel, Switzerland), Servier (Paris, France), and Takeda (Osaka, Japan). He has served on the speakers{\textquoteright} bureau of Eli Lilly, Gedeon Richter (Budapest, Hungary), Janssen Cilag (Neuss, Germany), Lundbeck, Roche, Servier, and Trommsdorf (Aachen, Germany). He has received grant support from Boehringer Ingelheim and Roche. He is co-founder of Pharma Image GmbH (D{\"u}sseldorf, Germany) and Brainfoods UG (Selfkant, Germany). Dr. Hiemke has received speaker{\textquoteright}s or consultancy fees from the following pharmaceutical companies: Janssen, Lilly and Servier. He is managing director of the psiac GmbH which provides an internet-based drug-drug interaction program for psychopharmacotherapy. Drs. Schoretsanitis, de Leon, Stegmann and Paulzen had no conflicts of interest during the last 12 months. Publisher Copyright: {\textcopyright} 2017 Elsevier B.V. and ECNP",

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AU - de Leon, Jose

AU - Haen, Ekkehard

AU - Stegmann, Benedikt

AU - Hiemke, Christoph

AU - Gründer, Gerhard

AU - Paulzen, Michael

N1 - Funding Information: Dr. Haen received speaker’s or consultancy fees from the following pharmaceutical companies: Servier, Novartis, and Janssen-Cilag. He is managing director of AGATE, a non-profit working group to improve drug safety and efficacy in the treatment of psychiatric diseases. Dr. Gründer has served as a consultant for Boehringer Ingelheim (Ingelheim, Germany), Cheplapharm (Greifswald, Germany), Eli Lilly (Indianapolis, IN, USA), Lundbeck (Copenhagen, Denmark), Ono Pharmaceuticals (Osaka, Japan), Roche (Basel, Switzerland), Servier (Paris, France), and Takeda (Osaka, Japan). He has served on the speakers’ bureau of Eli Lilly, Gedeon Richter (Budapest, Hungary), Janssen Cilag (Neuss, Germany), Lundbeck, Roche, Servier, and Trommsdorf (Aachen, Germany). He has received grant support from Boehringer Ingelheim and Roche. He is co-founder of Pharma Image GmbH (Düsseldorf, Germany) and Brainfoods UG (Selfkant, Germany). Dr. Hiemke has received speaker’s or consultancy fees from the following pharmaceutical companies: Janssen, Lilly and Servier. He is managing director of the psiac GmbH which provides an internet-based drug-drug interaction program for psychopharmacotherapy. Drs. Schoretsanitis, de Leon, Stegmann and Paulzen had no conflicts of interest during the last 12 months. Publisher Copyright: © 2017 Elsevier B.V. and ECNP

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AB - We aimed to explore the differences in the pharmacokinetics of risperidone between oral and long-acting injectable (LAI) formulations using a large database of therapeutic drug monitoring (TDM). Plasma concentrations of risperidone (RIS), its active metabolite (9-OH-RIS) and the active moiety (AM) (RIS+9-OH-RIS), their concentration-to-dose (C/D) ratios and ratio of RIS/9-OH-RIS (an index of CYP2D6 metabolic activity) were used to compare patients receiving risperidone orally (n = 851) and those treated with LAI RIS (n = 63). Patients taking CYP inducers or inhibitors or with liver/renal impairment were eliminated. Our study demonstrated that patients on LAI RIS, despite slightly higher RIS doses in the oral group, showed no significant differences in total AM or 9-OH-RIS. Conversely, RIS concentration, RIS C/D ratio and total C/D ratio were slightly higher in the LAI RIS group, reaching significance due to the large sample size. More importantly, the median ratio of RIS/9-OH-RIS was 0.52 in LAI RIS vs. 0.25 in the oral group, providing a significant difference (p < 0.001). After controlling for confounding factors, we replicated the RIS/9-OH–RIS ratio increases in patients with LAI RIS, probably reflecting a decrease in first-pass metabolism. More studies are required to establish the clinical use of TDM for patients on LAI RIS.

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Pharmacokinetics of risperidone in different application forms – Comparing long-acting injectable and oral formulations

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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