Schoretsanitis Georgios, Haen Ekkehard, Stegmann Benedikt, Hiemke Christoph, Gründer Gerhard, Paulzen Michael
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.
Clinical Pharmacology, Dept. of Psychiatry and Psychotherapy, Dept. of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
Schizophr Res. 2017 Jul;185:51-57. doi: 10.1016/j.schres.2016.12.016. Epub 2016 Dec 16.
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.
在一个自然样本中，理清吸烟、吸烟习惯与药代动力学模式之间的关联，如利培酮（RIS）、其活性代谢物9-羟基利培酮（9-OH-RIS）及活性部分（AM，即RIS + 9-OH-RIS）的血浆浓度。
比较治疗药物监测（TDM）数据库中吸烟者（n = 401）和非吸烟者（n = 292）的血浆浓度、RIS、9-OH-RIS和AM的剂量校正血浆浓度（C/D）。
利培酮的每日剂量差异显著，吸烟者接受的剂量高于对照组患者（p = 0.001）。活性部分、RIS和9-OH-RIS的血浆浓度未检测到差异（AM为p = 0.8，RIS为p = 0.646，9-OH-RIS为p = 0.538）。然而，代谢物（C/D 9-OH-RIS）和活性部分（C/D AM）的剂量校正浓度在组间差异显著（p = 0.002和p = 0.007）。将吸烟者分为中度吸烟者组（<20支/天）（RS1，n = 109）和重度吸烟者组（≥20支/天）（RS2，n = 135）后，非吸烟者与两组的比较仅显示中度吸烟者组9-OH-RIS的C/D值较低（p = 0.011），而其他药代动力学参数无差异。
除了众所周知的多环芳烃对CYP1A2活性的诱导作用外，吸烟可能也会对其他CYP同工酶产生影响。一种可能的解释是，吸烟对利培酮代谢可能有轻微的诱导作用，最有可能是通过CYP3A4。
