摘要
In the present study,we aimed to determine the pharmacokinetics(PK),pharmacodynamics(PD),adverse events(AEs),and their relationships in Chinese patients with schizophrenia after a single dose of long-acting risperidone.Schizophrenic patients(six females and seven males)were enrolled in this study.Serial blood samples were collected after drug administration during 63 d,and the drug concentrations were analyzed by LC-MS/MS.Safety and tolerance were evaluated by monitoring the AEs,changes in clinical laboratory results,12-lead ECG,vital signs,physical examination,and injection-site reactions.The extrapyramidal symptoms were evaluated using the ESRS.Efficacy was evaluated by the PANSS and BPRS.Twelve out of the 13 participants completed the trial.There were few clinically meaningful changes in mean clinical laboratory values,vital signs,or ECG parameters,except for the prolactin level and body weight.There were no serious AEs,and those observed were reversible.Significant clinical improvements in PANSS and PANSS-derived BPRS total scores were observed.The mean(standard deviation,coefficient of variation)values for these PK parameters were as follows:C_(max),8.954(8.059,90.0%)ng/mL;area under the curve AUC_(0-t),2453(1156,47.1%)ng·h/mL;AUC_(0-∞),2472(1160,46.9%)ng·h/mL;t_(max),830.0(min:744.0,max:984.0,11.8%)h;and t_(1/2),68.56(10.77,15.7%)h.The PK characteristics of long-acting risperidone showed a high level of inter-individual variation,while there were no clear correlations between PK,efficacy and AEs among the patients in the present study.
本研究旨在探讨在中国精神分裂症患者中应用单剂量长效利培酮注射液后的药代动力学、药效学、不良事件及其相互关系。精神分裂症患者(6名女性和7名男性)被纳入这项研究。给药后连续采血至63天,应用液质联用方法分析血浆药物浓度。通过监测不良事件、临床实验室结果变化、12导联心电图、生命体征、体格检查和注射部位反应来评价安全性和耐受性。采用锥体外系症状评定量表(ESRS)对锥体外系症状进行评估,采用阳性与阴性症状量表(PANSS)和简明精神病量表(BPRS)评价疗效。13名入组受试者中12人完成了本试验。除催乳素水平和体重外,平均临床实验室检验值、生命体征和心电图参数几乎未发生有临床意义的变化。无严重不良事件发生,所观察到的不良事件均是可逆的。观察到PANSS和PANSS衍生的BPRS总分均有显著改善。药代动力学参数的均值(标准差,变异系数)为:C_(max),8.954(8.059,90.0%)ng/mL;AUC_(0-t),2453(1156,47.1%)ng·h/mL;AUC_(0-∞),2472(1160,46.9%)ng·h/mL;t_(max),830.0(min:744.0,max:984.0,11.8%)h;t_(1/2),68.56(10.77,15.7%)h。长效利培酮的药代动力学特征在个体间存在较高的变异,而本研究中精神分裂症患者药代动力学、疗效、不良事件之间无明显相关性。
基金
Foundation items:The National Major Scientific and Technological Special Project for"Significant New Drug Development"during the Twelfth Five-year Planning Period of China(Grant No.2014ZX09303303).
