The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Behavioral Health Pavilion, 7559 263rd Street, Glen Oaks, NY, 11004, USA.
Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
Eur Arch Psychiatry Clin Neurosci. 2021 Dec;271(8):1437-1443. doi: 10.1007/s00406-021-01257-9. Epub 2021 Apr 5.
To investigate pharmacokinetic correlates of clinical response in patients treated with once-monthly paliperidone palmitate (PP1M) injections at steady state. Plasma concentrations and dose-adjusted-plasma concentrations (C/D) of paliperidone from a naturalistic therapeutic drug monitoring (TDM) database were compared between responders and non-responders using the Clinical Global Impressions-Improvement scale (CGI-I) ratings. Analyses were based on the non-parametric Mann-Whitney U test and the Pearson Chi-squared test (χ) with a significance level of 0.05. Subgroup analyses were performed separately in patients with schizophrenia spectrum, schizoaffective disorders and bipolar disorders. Comparing 93 responders with 80 non-responders, we detected no significant differences in the proportion of females, age, and body mass index (p's ranging 0.18-0.83); there were more smokers in the group of non-responders (p = 0.04), which also included more patients with bipolar disorders (p = 0.014). Despite the lack of differences for prescribed PP1M doses and dose intervals (p = 0.42 and p = 0.11, respectively), non-responders had higher paliperidone plasma concentrations and C/D levels (p = 0.033 and p = 0.021, respectively). Subgroup analyses did not yield differences for paliperidone plasma and C/D levels between non-responders and responders with schizophrenia spectrum (p = 0.099 and p = 0.14, respectively) and bipolar disorders (p = 0.95 and p = 0.75, respectively); dose-adjusted plasma concentrations were higher in non-responders compared to responders with schizoaffective disorders (p = 0.039), while no differences were reported for plasma levels (p = 0. 15). Our results show that paliperidone plasma concentrations over injection doses may be associated with patterns of clinical response suggesting potential utility of TDM as part of PP1M-based maintenance treatment.
研究在稳定状态下接受每月一次帕利哌酮棕榈酸酯（PP1M）注射治疗的患者中，临床反应的药代动力学相关性。使用临床总体印象-改善量表（CGI-I）评分，比较了来自自然治疗药物监测（TDM）数据库的帕利哌酮的血浆浓度和剂量调整后的血浆浓度（C/D）与应答者和无应答者之间的关系。分析基于非参数曼-惠特尼 U 检验和皮尔逊卡方检验（χ），显著性水平为 0.05。亚组分析分别在精神分裂症谱系、分裂情感障碍和双相障碍患者中进行。比较 93 名应答者和 80 名无应答者，我们没有发现女性比例、年龄和体重指数（p 值范围为 0.18-0.83）存在显著差异；无应答者组中吸烟者较多（p=0.04），其中还包括更多的双相障碍患者（p=0.014）。尽管 PP1M 剂量和剂量间隔的规定没有差异（p=0.42 和 p=0.11），但无应答者的帕利哌酮血浆浓度和 C/D 水平更高（p=0.033 和 p=0.021）。亚组分析显示，在精神分裂症谱系（p=0.099 和 p=0.14）和双相障碍（p=0.95 和 p=0.75）患者中，无应答者和应答者之间的帕利哌酮血浆和 C/D 水平没有差异；与应答者相比，无应答者的剂量调整后血浆浓度更高与分裂情感障碍（p=0.039），而血浆水平无差异（p=0.15）。我们的结果表明，注射剂量以上的帕利哌酮血浆浓度可能与临床反应模式相关，这表明 TDM 作为 PP1M 维持治疗的一部分可能具有潜在的效用。
