Effect of smoking on risperidone pharmacokinetics – A multifactorial approach to better predict the influence on drug metabolism

Schoretsanitis, Georgios; Haen, Ekkehard; Stegmann, Benedikt; Hiemke, Christoph; Gründer, Gerhard; Paulzen, Michael (2017). Effect of smoking on risperidone pharmacokinetics – A multifactorial approach to better predict the influence on drug metabolism. Schizophrenia Research, 185, pp. 51-57. Elsevier 10.1016/j.schres.2016.12.016

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Purpose 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. Methods 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). Results 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 (< 20 cigarettes/day) (RS1, n = 109) and a group of heavy smokers (≥ 20 cigarettes/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. Conclusions 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Translational Research Center

UniBE Contributor:

Schoretsanitis, Georgios

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0920-9964

Publisher:

Elsevier

Language:

English

Submitter:

Georgios Schoretsanitis

Date Deposited:

12 Apr 2017 10:30

Last Modified:

18 Jun 2017 01:30

Publisher DOI:

10.1016/j.schres.2016.12.016

PubMed ID:

27993531

BORIS DOI:

10.7892/boris.91625

URI:

https://boris.unibe.ch/id/eprint/91625

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