帕利哌酮棕榈酸盐多次给药的稳态血药浓度与临床安全性的研究

目的研究帕利哌酮棕榈酸盐在精神分裂症患者中多次给药的血浆药物浓度水平及其与治疗安全性的关系。方法 18名符合DSM-IV精神分裂症诊断患者经过第1,8,38 d的固定剂量注射后,每30 d进行一次剂量可变的药物注射,按照最后3针实际给予的药物剂量分组。于试验第8,11,14,17,21,28,38,68,98,128,158,188 d采血,高效液相色谱法测定血浆中帕利哌酮浓度,临床症状在试验第1 d和188 d用PANSS评分,安全性则通过不良事件监测、生命体征监测、实验室检查以及锥体外系反应量表评估,用SPSS软件分析数据。结果17名最终完成试验的患者分为75 mg eq.(n=5)、100 mg eq.(n=9)、150 mgeq.(n=3)3组,各组的稳态血药浓度为(23.42±11.95),(24.52±12.44),(16.92±6.53)ng.mL-1,注射后的峰浓度出现在第11～18 d,平均为17 d。11例患者共出现17例次不良事件,程度均为轻中度。结论给药后,帕利哌酮棕榈酸盐各剂量组间稳态浓度无差异,但个体差异明显。药物剂量与不良反应间未见关联。

Plasma concentrations of intramuscular paliperidone palmitate and the relationship between the dose and clinical safety

Objective To analyze the plasma concentrations of paliperidone palmitate and the relationship between the dose and clinical safety.Methods Eighteen patients met the DSM-IV diagnosis of schizophrenia received injection of paliperidone palmitate on day 1,8,38 of fix-dose,and every 30 days of flexible-dose.The groups were divided according to the last three actual-given doses.The blood were taken on day 8th,11th,14th,17th,21st,28th,38th,68th,98th,128th,158th and 188th.The plasma concentrations of paliperidone palmitate were detected by HPLC method.The clinical symptom was measured by PANSS on day 1st and 188th.Clinical safety was evaluated by monitoring of adverse events and vital signs,lab tests and extrapyramidal side effects scale.All the data were analyzed by SPSS.Results Seventeen patients completed the project,and were divided into 3 groups: 75 mg eq.(n=5),100 mg eq.(n=9),and 150 mg eq.(n=3).The mean plasma concentrations of each group were(23.42±11.95),(24.52±12.44),(16.92±6.53) ng·mL-1,the peak concentrations reached at day 11th-18th,and the average time was day17th.There were 11 subjects reported totally 17 cases of adverse reactions,which were mild to moderate.Conclusion The steady-state concentrations of paliperidone palmitate have no difference among the groups,while individual differences are significant.And the drug doses are not associated with the adverse reactions.