氯氮平口腔崩解片在精神分裂症患者体内的生物等效性

Study on bioequivalence of clozapine orally disintegrating tablets in patients with schizophrenia

目的:研究受试制剂氯氮平口腔崩解片和参比制剂氯氮平片在精神分裂症患者体内的药动学过程并判断两制剂是否具有生物等效性。方法:采用随机双周期,自身交叉设计,20名受试者分别口服受试制剂或参比制剂100 mg,q12 h,连续服用10 d后采集血样,HPLC-MS/MS法测定血浆中氯氮平的浓度,DAS软件求算有关药动学参数和相对生物利用度。结果:受试制剂和参比制剂的主要药动学参数Cmax分别为(540.0±228.3)μg.L-1、(534.1±205.7)μg.L-1,tmax分别为(2.0±0.9)h、(2.0±0.9)h,t1/2分别为(9.7±3.6)h、(11.4±6.3)h,AUCss分别为(3753.9±1371.5)μg.h.L-1、(3 819.4±1 591.8)μg.h.L-1;以AUCss计,受试制剂的相对生物利用度为(101.2±19.4)%。20名受试者口服受试制剂口感良好,没有沙砾感,崩解时限为(34.6±10.2)s。结论:两种制剂生物等效。

OBJECTIVE To study the bioequivalence of orally disintegrating tablets and tablets of clozapine in patients with schizophrenia. METHODS The study was a randomized, two-way crossover design in which patients with schizophrenia received test preparation or reference preparation 100 mg twice daily for 10 days. Plasma concentrations of clozapine were determined by HPLC MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated by DAS. RESULTS The main pharmacokinetic parameters of test preparation or reference preparation were as follows： Cmax were（540. 0 ±228. 3） and （534. 1 ± 205.7）μg·h·L-1;tmax were（2. 0 ±0. 9） and （2. 0 ± 0. 9）h;t1/hn were（9. 7±3.6）and（11.4 ± 6. 3）h. AUCss were（3 753.9 ± 1 371.5）and（3 819. 4 ± 1 591.8）μg·h·L-1 , respectively. The mean relative bioavailability of test preparation was（101.2 ±19. 4） %, according to AUCss. CONCLUSION The statistical analysis shows the two preparations are bioequivalent.