Spina E, Avenoso A, Facciolà G, Salemi M, Scordo M G, Ancione M, Madia A G, Perucca E
Institute of Pharmacology, University of Messina, Policlinico Universitario, Italy.
Psychopharmacology (Berl). 2001 Jan 1;153(2):238-43. doi: 10.1007/s002130000576.
Evaluation of relationships between serum antipsychotic drug concentrations and clinical response may provide valuable information for rational dosage adjustments. For risperidone, this relationship has been little investigated to date.
To assess the relationship between plasma concentrations of risperidone and its active 9-hydroxy-metabolite (9-OH-risperidone) and clinical response in schizophrenic patients who experienced an acute exacerbation of the disorder.
Forty-two patients (30 males, 12 females, age 24-60 years) were given risperidone at dosages ranging from 4 to 9 mg/day for 6 weeks. The design of the study was open and risperidone dosage could be adjusted individually according to clinical response. Steady-state plasma concentrations of risperidone and its 9-hydroxymetabolite were measured after 4 and 6 weeks using a specific HPLC assay. Psychopathological state was assessed at baseline and at weeks 2, 4, and 6 by means of the positive and negative syndrome scale (PANSS), and patients were considered responders if they showed a greater than 20% reduction in total PANSS score at final evaluation compared with baseline.
Mean plasma concentrations of risperidone, 9-OH-risperidone, and active moiety (sum of risperidone and 9-OH-risperidone concentrations) did not differ between responders (n = 28) and non-responders (n = 14). No correlation between plasma levels and percent decrease in total PANSS score was found for risperidone (rs = -0.187, NS), 9-OH-risperidone (rs = 0.246, NS), and active moiety (rs = 0.249, NS). Active moiety concentrations in plasma were higher (P < 0.001) in patients developing clinically significant parkinsonian symptoms (n = 7) than in those with minimal (n = 7) or no drug-induced parkinsonism (n = 28).
In chronic schizophrenic patients experiencing an acute exacerbation of the disorder, plasma levels of risperidone and its active metabolite correlate with the occurrence of parkinsonian side effects, whereas no significant correlation appears to exist with the degree of clinical improvement.
评估血清抗精神病药物浓度与临床反应之间的关系可为合理调整剂量提供有价值的信息。对于利培酮而言，迄今为止对这种关系的研究很少。
评估利培酮及其活性9-羟基代谢物（9-OH-利培酮）的血浆浓度与经历该疾病急性加重的精神分裂症患者临床反应之间的关系。
42例患者（30例男性，12例女性，年龄24 - 60岁）接受利培酮治疗，剂量范围为4至9毫克/天，持续6周。该研究设计为开放性，利培酮剂量可根据临床反应进行个体化调整。在第4周和第6周使用特定的高效液相色谱法测定利培酮及其9-羟基代谢物的稳态血浆浓度。在基线以及第2、4和6周通过阳性和阴性症状量表（PANSS）评估精神病理状态，如果患者在最终评估时与基线相比PANSS总分降低超过20%，则被视为有反应者。
有反应者（n = 28）和无反应者（n = 14）之间利培酮、9-OH-利培酮和活性部分（利培酮和9-OH-利培酮浓度之和）的平均血浆浓度无差异。利培酮（rs = -0.187，无显著性差异）、9-OH-利培酮（rs = 0.246，无显著性差异）和活性部分（rs = 0.249，无显著性差异）的血浆水平与PANSS总分降低百分比之间均未发现相关性。出现具有临床意义的帕金森症状的患者（n = 7）血浆中的活性部分浓度高于仅有轻微症状（n = 7）或无药物性帕金森症的患者（n = 28）（P < 0.001）。
在经历该疾病急性加重的慢性精神分裂症患者中，利培酮及其活性代谢物的血浆水平与帕金森副作用的发生相关，而与临床改善程度似乎无显著相关性。
