氯氮平的药代动力学及其临床应用

目的：研究首发未服药精神分裂症病人的药代动力学特征，以及氯氮平的血药浓度与疗效和副反应的.:应运地首发未用过抗精神病药的28例病人，空腹12小时后给一次口服氯氮平50mg,在给药后0．5、2、5、8、12、24和36小时取血，求得氯氮平的药代动力学参数。按照个体参数计算其服药量，比较4周未、12周未实际服药剂量低于计算值组和实际服药剂量高于计算值组两组疗效及副反应，比较77例服氯氮平病人4周末、12周末血药浓度范围在200－600ng/ml以及超出此范围的两组的疗效和副反应，并比较脑电图中度（或中度以上）异常组与脑电图正常（或轻度异常）组血药浓度、服药剂量、MINIDOTES副反应总分。结果：氯氮平吸收相的半衰期平均1．13小时，消除相的半衰期平均9．50小时，口服氯氮平吸较收快，平均3．44小时达高峰浓度，4周末实际服药剂量低于计算值组和实际服药剂量高于计算值组两组血药浓度和服药剂量无显著差异；但平均血药浓度较高组的副反应则显著增加，脑电图中度以上异常组血药浓度显著高于正常或轻度异常组。结论：氯氮平以应（如脑电图异常）与血药浓度的增加有关。

The pharmacokinetics of clozapine and it's clinical utilization

Objective:To evaluate the pharmacokinetics of clozapine in the first episode and drug naive schizophrenia or schizophreniform psychosis and the relationship between the blood level of clozapine and the efficacy or side effects. Method:Twenty eight patients which never been used antipsychotic drugs were entered into the study. The first 50mg oral dose of clozapine was given after fasting for 12 hours. Blood samples were taken at 0 5,2,5,8,12,24 and 36 hours after giving clozapine to measure it's blood level and calculate the parameters, then used pharmacokinetic parameters to get the predictable dosage of clozapine. We compared the effects and side effects between the patients using less than predictable dosage and more than it, and the efficacy and side effects were also compared between the patients whose clozapine blood levels were in the range of 200~600ng/ml and out of this range, in addition, we compared the blood levels, dosage, total scores of side effects according to EEG. Results:The half life of absorption phase and elimination phase were 1 13 hr and 9 50 hr respectively, plasma peak concentration reached at 3 44 hr. After 4 weeks, no significant differences were founded in blood levels of clozapine and the dosage that patients taking actually between different predictable dosage groups. Conclusion:The side effects of clozapine (eg. abnormal EEG) is associated with it's increase of blood level.