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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)130-137
Number of pages8
JournalEuropean Neuropsychopharmacology
Volume28
Issue number1
DOIs
StatePublished - 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)

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