Michael Paulzen1, Ekkehard Haen2, Benedikt Stegmann2, Christoph Hiemke3, Gerhard Gründer1, Sarah E Lammertz1, Georgios Schoretsanitis4. 1. Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, and JARA - Translational Brain Medicine, Pauwelsstraße 30, 52074 Aachen, Germany. 2. Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Universitätsstrasse 84, 93053 Regensburg, Germany. 3. Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany. 4. Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, and JARA - Translational Brain Medicine, Pauwelsstraße 30, 52074 Aachen, Germany; University Hospital of Psychiatry, Bolligenstrasse 111, 3000 Bern, Switzerland. Electronic address: george.schor@gmail.com.
Abstract
OBJECTIVE: We sought to unravel the influence of body weight and body mass index (BMI), both consistently reported as pharmacokinetic relevant parameters, on metabolism of risperidone in a naturalistic sample. METHODS: Conducting non parametrical tests we sought for correlations between plasma concentrations of RIS, 9-OH-RIS and AM and body weight and BMI in patients out of a therapeutic drug monitoring (TDM) database. Further, we stratified patients to three groups based upon BMI values and compared drug concentrations between groups. RESULTS: Although body weight failed to correlate with pharmacokinetic parameters, BMI was positively correlated with plasma concentrations of the active metabolite (9-OH-RIS) (rs=0.121, p=0.002) and active moiety (sum of RIS+9-OH-RIS) (rs=0.128, p=0.001) as well as dose adjusted plasma concentrations of the active moiety (rs=0.08, p=0.04). The comparison of pharmacokinetic parameters between different BMI groups yielded lower plasma concentrations of 9-OH-RIS in patients with low BMI (<20kg/m2) and higher plasma concentrations of the active moiety in obese patients (BMI ≥30kg/m2) when compared with the control group (30>BMI≥20kg/m2). By comparing low vs. high BMI patients, the latter group showed higher 9-OH-RIS plasma concentrations. CONCLUSIONS AND LIMITATIONS: Considerable alterations in metabolism of risperidone were detected when comparing obese and cachectic patients with the control group in alignment with the positive correlation between BMI values and plasma concentrations of the active metabolite and active moiety as well as dose adjusted plasma concentrations of the active moiety. We suggest changes in CYP2D6 or CYP3A4 activity or differences in P-glycoprotein function in obese patients with greater BMI as a plausible mechanism underlying these alterations.
OBJECTIVE: We sought to unravel the influence of body weight and body mass index (BMI), both consistently reported as pharmacokinetic relevant parameters, on metabolism of risperidone in a naturalistic sample. METHODS: Conducting non parametrical tests we sought for correlations between plasma concentrations of RIS, 9-OH-RIS and AM and body weight and BMI in patients out of a therapeutic drug monitoring (TDM) database. Further, we stratified patients to three groups based upon BMI values and compared drug concentrations between groups. RESULTS: Although body weight failed to correlate with pharmacokinetic parameters, BMI was positively correlated with plasma concentrations of the active metabolite (9-OH-RIS) (rs=0.121, p=0.002) and active moiety (sum of RIS+9-OH-RIS) (rs=0.128, p=0.001) as well as dose adjusted plasma concentrations of the active moiety (rs=0.08, p=0.04). The comparison of pharmacokinetic parameters between different BMI groups yielded lower plasma concentrations of 9-OH-RIS in patients with low BMI (<20kg/m2) and higher plasma concentrations of the active moiety in obesepatients (BMI ≥30kg/m2) when compared with the control group (30>BMI≥20kg/m2). By comparing low vs. high BMI patients, the latter group showed higher 9-OH-RIS plasma concentrations. CONCLUSIONS AND LIMITATIONS: Considerable alterations in metabolism of risperidone were detected when comparing obese and cachectic patients with the control group in alignment with the positive correlation between BMI values and plasma concentrations of the active metabolite and active moiety as well as dose adjusted plasma concentrations of the active moiety. We suggest changes in CYP2D6 or CYP3A4 activity or differences in P-glycoprotein function in obesepatients with greater BMI as a plausible mechanism underlying these alterations.
Authors: R Taurines; S Fekete; A Preuss-Wiedenhoff; A Warnke; C Wewetzer; P Plener; R Burger; M Gerlach; M Romanos; K M Egberts Journal: J Neural Transm (Vienna) Date: 2022-03-18 Impact factor: 3.850
Authors: Jose Rodríguez-Morató; Albert Goday; Klaus Langohr; Mitona Pujadas; Ester Civit; Clara Pérez-Mañá; Esther Papaseit; Jose Manuel Ramon; David Benaiges; Olga Castañer; Magí Farré; Rafael de la Torre Journal: Sci Rep Date: 2019-12-31 Impact factor: 4.379