盐酸齐拉西酮在中国健康志愿者中的药代动力学研究

Pharmacokinetics of ziprasidone capsule in Chinese healthy volunteers

目的评价国产盐酸齐拉西酮胶囊的人体药代动力学特点;初步评价国产盐酸齐拉西酮胶囊的安全性。方法采用HPLC法测定血浆中齐拉西酮浓度。10位男性健康受试者进食时单剂量口服40mg盐酸齐拉西酮胶囊。于服药前及服药后0.5、1、2、3、4、5、6、8、10、12、24、36、48小时采集5m l血样。抗凝处理取血浆,-20℃保存,用于血药浓度的测定。安全性评价包括体检、实验室检查(心电图、血常规、生化常规及尿常规等)及不良事件的记录。结果主要药动学参数:Cm ax为(175.0±63.73)ng/m l;Tm ax为(3.80±1.32)h;MRT为(9.37±1.53)h;t1/2为(6.10±1.65)h;Ka为0.1831±0.0708/h;Kel为0.1219±0.0349/h;Vd为(685.3±325.4)L;C l为(83.30±34.50)L/h;AUC0→t为(1312±261.3)ng/m l/h,AUC0→∝为(1339±261.1)ng/m l/h。药物不良事件主要为嗜睡、口干、头昏、静坐不能、体位性低血压等,程度多为轻至中度,均能在短时间内缓解。结论研究结果显示了国产盐酸齐拉西酮在中国人中药代动力学特点,单剂量口服胶囊40mg是安全的。

Objective： To evaluate the pharmacokinetics characteristics and safety of national hydrochloric ziprasidone capsule in Chinese healthy controllers. Methods： The concentration of ziprasidone in plasma were determined by a validated high - performance liquid chromatography （HPLC） method. Results ： The main pharmacokinetic parameters were as follows ： Cmax was （ 175.0 ± 63.73 ） ng/ml ; Tmax was （ 3.80 ± 1.32） h;MRT was （9.37 ± 1.53 ）h;t1/2 was （6.10 ± 1.65 ）h;Ka was （0. 1831 ± 0.0708）h-1 ;Kel was （0.1219 ± 0. 0349） h ^-1 ; Vd was （ 685.3 ± 325.4 ） L; Cl was （ 83.30 ± 34.50） L/h ; AUC0→t, was （ 1312 ± 261.3） ng/ml/h, AUC0→x was （1339±261. 1 ）ng/ml/h. The main side effects were mild to moderate somnolence, dry mouth, dizziness, akathisia and postural hypotension etc. and they could be remission in a short time. Conclusion： The study showed the pharmacokinetics characteristics of national hydrochloric ziprasidone capsule. Singe dose of 40mg/day of ziprasdione was safe for Chinese.