帕利哌酮治疗精神分裂症的血药浓度与临床疗效研究

Correlation between Paliperidone plasma concentration and clinical efficacy in treatment of schizophrenia

目的探讨帕利哌酮治疗精神分裂症的血药浓度与剂量、临床疗效及副反应的关系。方法采用超高效液相色谱串联质谱法分别于治疗后1、2及4周末检测精神分裂症患者体内帕利哌酮血药浓度;于基线期、治疗后1、2及4周末采用阳性与阴性症状量表(PANSS)评定疗效,治疗时出现的症状量表(TESS)评定副反应;于基线期和治疗后4周末行血常规、尿常规、肝肾功能、心电图及泌乳素检查。结果治疗后1、2及4周末的服药剂量分别为(7.24±1.50),(8.89±1.29)和(9.63±1.77),与相应时间的血药浓度(18.64±7.93),(25.44±10.71)和(27.65±13.89)呈正相关(P<0.05);帕利哌酮血药浓度(30.91±17.99)与女性患者的血清泌乳素(117.9±50.66)相关(P<0.05);未发现帕利哌酮血药浓度与PANSS减分率、TESS量表以及体重增加值相关(P>0.05);有效组与无效组间、出现锥外系反应组患者与未出现锥外系反应组间血药浓度比较差异皆均无统计学意义(P>0.05)。结论帕利哌酮的血药浓度可能与服药剂量呈非线性正相关;帕利哌酮的血药浓度与女性患者的血清泌乳素水平呈正相关。

Objective To examine the correlations of Paliperidone plasma concentration with drug dose, clinical efficacy and side effects in patients with schizophrenia. Methods The patients with schizophrenia were treated by Paliperidone. The plasma concentration was monitored by high-performance liquid chromatography-tandem mass spectrometry （RP-HPLC） at the end of the 1st, 2nd and 4th week. The clinical efficacy was evaluated using the Positive and Negative Syndrome Scale （PANSS） and the side effects were evaluated by the Treatment Emergent Symptom Scale （TESS） at the baseline and at the end of the 1st, 2nd and 4th week after treatment. The blood routine, urinalysis, liver and kidney functions, electrocardiogram and prolactin level detection were done at baseline and the 4th weekend after treatment. Results The Paliperidone dosages [（7.24 ±1.50）, （8.89 ± 1.29）, （9.63 ± 1.77）] were positively correlated with the blood concentrations [（18.64 ±7.93）, （25.44 ± 10.71）, （27.65 ±13.89）] at the end of the 1st, 2nd and 4th week after treatment （P 〈 0.05）. The plasma concentration of Paliperidone was correlated with serum prolaetin level in the female patients （P 〈 0.05）. The plasma concentration of Palipefidone was not correlated with the reduction rate of PANSS scores, TESS or the value of weight gain （P 〉 0.05）. There was no significant difference in the plasma concentration of Paliperidone between the effective and ineffective groups or between the extrapyramidal reaction group and the non-extrapyramidal reaction group （P 〉 0.05）. Conclusions There is a positively nonlinear correlation between the plasma concentration and the dose of Paliperidone. There is a positive correlation between the Paliperidone plasma concentration and serum prolaetin level.