title: Effect of smoking on risperidone pharmacokinetics - A multifactorial approach to better predict the influence on drug metabolism.
abstract: To disentangle an association between tobacco smoking, smoking habits and pharmacokinetic patterns such as plasma concentrations of risperidone (RIS), its active metabolite 9-hydroxyrisperidone (9-OH-RIS) and the active moiety, AM, (RIS+9-OH-RIS) in a naturalistic sample.
  
  
  
  Plasma concentrations, dose adjusted plasma concentrations (C/D) of RIS, 9-OH-RIS and AM in patients out of a therapeutic drug monitoring (TDM) database were compared between smokers (n=401) and non-smokers (n=292).
  
  
  
  Daily dosage of risperidone differed significantly with smokers receiving higher doses than patients in the control group (p=0.001). No differences were detected in plasma concentrations of the active moiety, RIS and 9-OH-RIS (p=0.8 for AM, p=0.646 for RIS and p=0.538 for 9-OH-RIS). However, dose corrected concentrations (C/D) of metabolite (C/D 9-OH-RIS) and active moiety (C/D AM) differed between significantly between groups (p=0.002 and p=0.007). After stratifying smokers to a group of moderate smokers (<20cigarettes/day) (RS1, n=109) and a group of heavy smokers (≥20cigarettes/day) (RS2, n=135), the comparison between non-smokers and both groups only showed lower values of C/D for 9-OH-RIS (p=0.011) for the group of moderate smokers while other pharmacokinetic parameters did not differ.
  
  
  
  Apart from the well-known induction of CYP1A2 activity by polycyclic aromatic hydrocarbons, smoking might exert an effect on other CYP isoenzymes as well. A possible interpretation proposes a slight inducing effect of smoking on risperidone metabolism most likely via CYP3A4.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, RWTH Aachen University, Aachen, Germany; University Hospital of Psychiatry, Bern, Switzerland. Electronic address: george.schor@gmail.com.
authors.forename: Georgios
authors.initials: G
authors.lastname: Schoretsanitis
authors.affiliation: Clinical Pharmacology, Dept. of Psychiatry and Psychotherapy, Dept. of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Haen
authors.affiliation: Clinical Pharmacology, Dept. of Psychiatry and Psychotherapy, Dept. of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Stegmann
authors.affiliation: Department of Psychiatry and Psychotherapy, Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, RWTH Aachen University, Aachen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, RWTH Aachen University, Aachen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Paulzen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate / Q000097:blood*; D012189:Retrospective Studies; D018967:Risperidone / Q000097:blood* / Q000627:therapeutic use*; D012720:Severity of Illness Index; D012907:Smoking / Q000097:blood* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone; D000068882:Paliperidone Palmitate
keywords: Cytochrome P450; Pharmacokinetics; Plasma concentration; Risperidone; Smoking; Therapeutic drug monitoring