氯氮平口腔崩解片在健康人体的药动学研究

Pharmacokinetics of Clozapine Orally Disintegrating Tablets in Healthy Volunteers

目的建立快速、灵敏的氯氮平人体内血药浓度的液相色谱串联质谱测定法,并对20名健康志愿者口服氯氮平口腔崩解片后在人体内的药动学过程进行研究。方法20名健康志愿者单剂量口服给药25mg后,分别于给药前和给药后0.25、0.5、0.75、1、1.5、2、3、4、6、8、10、12、24、36及60h采集血样。用高效液相色谱串联质谱法测定血浆中氯氮平的浓度,并采用PKS药动学程序对试验数据进行处理,求算有关药动学参数。结果单剂量口服给药氯氮平口腔崩解片25mg后,其药-时曲线拟合符合二室模型,T1/2、Tmax、Cmax、AUC0-60、AUC0-∞分别为(14.54±3·59)h、(0.94±0.30)h、(68·53±16.88)μg/L,(555.2±183.2)μg/(L·h)、(588.5±199.6)μg/(L·h)。结论试验建立的氯氮平人体内血药浓度测定方法灵敏、可靠、简便;氯氮平口腔崩解片单剂量给药后在中国健康人体内的药动学行为与文献报道基本一致。

Objective To develop a rapid and sensitive HPLC- MS/MS method for the analysis of clozapine in human plasma, and to study the pharmacokinetics characteristics of clozapine orally disintegrating tablets after a single oral dose of 25 mg in healthy volunteers. Methods A single oral dose of 25 mg clozapine orally disintegrating tablets was given to 20 healthy volunteers. Blood samples were taken for detecting plasma concentration before dosing and at 0. 25, 0.5, 0. 75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 60 h after a single oral 25 mg. A HPLC - MS/MS method was used to assay the concentration of clozapine in plasma. The pharmacokinetic parameters were evaluated with PKS program. ResultsThe concentrations of clozapine in plasma were fitted with a two-compartment model. The main pharmacokinetic parameters of clozapine by oral administration were as follows ： T1/2 was （ 14. 54 ± 3.59 ） h, Tmax was （0. 94 ± 0. 30） h, Cmax was（68.53 ± 16. 88） μg/L, AUC0-60was（555.2 ± 183.2） μg/L. h, and AUC0-∞ was （588.5 ± 199.6） μg/L · h. Conclusion The analytical method appeared to be accurate, sensitive, and convenient. The pharmacokinetic characteristicof clozapine orally disintegrating tablet is similar to the reports.