title: Body mass index (BMI) but not body weight is associated with changes in the metabolism of risperidone; A pharmacokinetics-based hypothesis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, and JARA - Translational Brain Medicine, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Paulzen
authors.affiliation: Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Universitätsstrasse 84, 93053 Regensburg, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Haen
authors.affiliation: Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Universitätsstrasse 84, 93053 Regensburg, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Stegmann
authors.affiliation: 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.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, and JARA - Translational Brain Medicine, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, and JARA - Translational Brain Medicine, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lammertz
authors.affiliation: 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.
authors.forename: Georgios
authors.initials: G
authors.lastname: Schoretsanitis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics*; D015992:Body Mass Index; D001835:Body Weight; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D000068882:Paliperidone Palmitate / Q000097:blood / Q000493:pharmacokinetics*; D018967:Risperidone / Q000097:blood / Q000493:pharmacokinetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone; D000068882:Paliperidone Palmitate
keywords: BMI; Body mass index; Body weight; Drug metabolism; Pharmacokinetics; Psychopharmacology; Schizophrenia