左羟丙哌嗪含片人体相对生物利用度及等效性研究

Relative bioavailability and bioequivalence of levodropropizine buccal tablets

目的研究左羟丙哌嗪含片的相对生物利用度与生物等效性。方法采用2×2随机交叉试验设计,分别给予18名健康男性受试者试验制剂左羟丙哌嗪含片或参比制剂左羟丙哌嗪片60 mg,采用液质联用（LC-MS）测定血药浓度。利用DAS Ver 1.0计算药物动学参数并评价其生物等效性。结果参比制剂与试验制剂的达峰浓度（Cm ax）分别为（209.4±32.1）μg.L^-1和（231.4±36.1）μg.L^-1;0~12 h药时曲线下面积（AUC0→12）分别为（654.9±152.1）μg.h^-1.L^-1和（663.8±145.2）μg.h^-1.L^-1;0→∞药时曲线下面积（AUC0→∞）分别为（683.5±156.4）μg.h^-1.L^-1和（693.5±153.6）μg.h.L^-1。结论试验制剂对参比制剂的相对生物利用度（以AUC0→12作为评价依据）为102%±5%（95%-114%）,二者具有生物等效性。

Objective To study the relative bioavailability and bioequivalence of levodropropizine buccal tablets. Methods Oral dose （60 mg of levodropropizine buccal tablet or 60 mg of levodropropizine tablet） was given to 18 healthy male volunteers according to a randomized crossover design（2 × 2）. The concentrations of levodropropizine in plasma were determined by LC-MS. With DAS Ver 1.0,the pharmacokinetic parameters were calculated and the bioequvivalence was estimated. Results The main pharmacokinetics parameters of levodropropizine tablet and levodropropizine buccal tablet were as follow： peak concentration （ Cmax ） was （209.4±32. 1 ） μg ·L^-1 vs （231.4 ±36.1 ） μg·L^-1 ; AUC0→12 was （654.9 ±152.1 ） μg · h·L^ -1 vs （663.8±145.2） μg·h ·L^-1; AUC0→∞ was （683.5±156.4） μg· h· L^-1 vs （ 693.5±153.6 ） μg·h ·L^-1. Conclusion The relative bioavailability of levodropropizine buccal tablets and levodropropizine tablet was 102%±5% （95% -114% ） （based on AUC0→12 ）, and they have bioequivalence.