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 |
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Pages (from-to) | 130-137 |
Number of pages | 8 |
Journal | European Neuropsychopharmacology |
Volume | 28 |
Issue number | 1 |
DOIs | |
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)