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Effect of smoking on risperidone pharmacokinetics - A multifactorial approach to better predict the influence on drug
Georgios Schoretsanitis1, Ekkehard Haen2, Benedikt Stegmann2
1Department 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.
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 (<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.
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.
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