Schoretsanitis Georgios, Haen Ekkehard, Hiemke Christoph, Gründer Gerhard, Stegmann Benedikt, Schruers Koen R J, Veselinovic Tanja, Lammertz Sarah E, Paulzen Michael
aDepartment of Psychiatry, Psychotherapy and Psychosomatics, and JARA - Translational Brain Medicine, RWTH Aachen University, Aachen bClinical Pharmacology, Departments of Psychiatry and Psychotherapy, and Pharmacology and Toxicology, University of Regensburg, Regensburg cDepartment of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Mainz, Germany dSchool for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands eUniversity Hospital of Psychiatry, Bern, Switzerland.
Int Clin Psychopharmacol. 2016 Sep;31(5):259-64. doi: 10.1097/YIC.0000000000000131.
Antipsychotic drugs can induce various undesirable adverse motor reactions, such as extrapyramidal side effects (EPS). A widely accepted pharmacodynamic mechanism underlying EPS includes an increase in striatal D2-receptor occupancy. However, less is known about the pharmacokinetic background of EPS. The aim of this study was to analyze in-vivo possible pharmacokinetic patterns underlying biperiden-treated EPS in risperidone (RIS)-medicated patients. A large therapeutic drug monitoring database containing plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone (9-OH-RIS) of 2293 adult inpatients and outpatients was analyzed. Two groups were compared: a group receiving RIS (n=772) and a group comedicated with biperiden (n=68). Plasma concentrations, dose-adjusted plasma concentrations (C/D) of RIS, 9-OH-RIS, and active moiety (AM) (RIS+9-OH-RIS) as well as ratios of concentrations for metabolite to parent drug (9-OH-RIS/RIS) were computed. We compared the plasma concentrations of the different compounds between the two groups considering the prescription of biperiden as an indirect report of EPS. The daily dosage of RIS did not differ between groups. No differences were detected in case of plasma concentrations and C/D of RIS and active metabolite between the groups. However, plasma concentrations of the AM were significantly higher in the comedicated group (P=0.032) and showed a trend in terms of the active metabolite 9-OH-RIS (P=0.053). Data indicate enhanced AM plasma concentrations of RIS in patients comedicated with biperiden as an EPS treatment. This might underscore an association between higher plasma concentrations of the AM and treatment-requiring EPS.
抗精神病药物可诱发各种不良的运动不良反应，如锥体外系副作用（EPS）。EPS背后被广泛接受的药效学机制包括纹状体D2受体占有率增加。然而，关于EPS的药代动力学背景知之甚少。本研究的目的是分析在接受利培酮（RIS）治疗的患者中，苯海索治疗EPS可能的体内药代动力学模式。分析了一个大型治疗药物监测数据库，其中包含2293例成年住院患者和门诊患者的RIS及其代谢物9-羟基利培酮（9-OH-RIS）的血浆浓度。比较了两组：一组接受RIS治疗（n = 772），另一组联合使用苯海索（n = 68）。计算了RIS、9-OH-RIS和活性部分（AM）（RIS + 9-OH-RIS）的血浆浓度、剂量调整后的血浆浓度（C/D）以及代谢物与母体药物的浓度比（9-OH-RIS/RIS）。我们将两组之间不同化合物的血浆浓度进行了比较，将苯海索的处方作为EPS的间接报告。两组之间RIS的每日剂量没有差异。两组之间RIS和活性代谢物的血浆浓度及C/D均未检测到差异。然而，联合用药组中AM的血浆浓度显著更高（P = 0.032），并且在活性代谢物9-OH-RIS方面呈现出一种趋势（P = 0.053）。数据表明，联合使用苯海索作为EPS治疗的患者中，RIS的AM血浆浓度升高。这可能强调了AM较高的血浆浓度与需要治疗的EPS之间的关联。
