国产与进口班布特罗片的人体生物等效性研究

Bioequivalence of domestic and imported bambuterol tablets in healthy volunteers

目的:研究国产班布特罗口腔崩解片在人体的相对生物利用度,并与进口片比较,评价两者生物等效性。方法:20例健康男性志愿者随机交叉单剂量口服国产盐酸班布特罗口腔崩解片(受试制剂)或进口盐酸班布特罗片(参比制剂)20 mg后,采用液相色谱串联质谱法测定血浆中班布特罗及其代谢产物特布他林的血药浓度,用DAS 2.0软件计算药代动力学参数,并评价其生物等效性。结果:受试制剂和参比制剂药代动力学参数为:Cmax(6.22±1.51)和(5.96±1.39)ng.mL-1;Tmax(2.52±0.72)和(2.70±0.86)h;t1/2(11.06±3.60)和(10.64±2.24)h;AUC0～72 h(56.69±16.82)和(52.86±14.57)ng.h.mL-1。特布他林药代动力学参数:Cmax(10.04±2.92)和(9.38±2.87)ng.mL-1;Tmax(4.35±1.04)和(4.60±1.14)h;t1/2(19.60±4.26)和(18.27±4.22)h;AUC0～72 h(199.60±68.89)和(179.55±50.18)ng.h.mL-1。国产盐酸班布特罗口腔崩解片单次给药后的相对生物利用度为(107.4±16.9)%(班布特罗),(110.9±18.6)%(特布他林)。结论:国产班布特罗口腔崩解片与进口班布特罗片在人体内生物等效。

Objective： To investigate the relative bioavailability of domestic bambuterol orally disintegrating tablets in healthy volunteers, and evaluate the bioequivalence of domestic and imported bambuterol tablets. Methods： A randomized crossover design was performed in 20 healthy male volunteers. A single oral dose （20 mg） of domestic bambuterol orally disintegrating tablets （test formulation） or imported bambuterol tablets （reference formulation） was administrated. Plasma concentrations of bambuterol and terbutaline were measured by liquid chroma-tography mass spectrometry. The pharmacokinetic parameters were calculated by DAS software and the bioequivalence was evaluated. Results： The main pharmacokinetic parameters of test and reference formulations were as follows. For bambuterol, Cmax was （6.22±1.51, test） and （5.96±1.39, reference） ng·mL-1 ; Tmax was （2.52 ± 0.72） and （2.70±0.86） h; t1/2was （11.06±3.60） and （10.64±2.24） h; AUC0-72hwas （56.69±16.82） and （52.86±14.57） ng·h·mL-1. Forterbutaline, Cmax WaS （10.04±2.92） and （9.38±2.87） ng·mL-1; Tmax was （4.35±1.04） and （4.60±1.14） h; t1/2 was （19.60±4.26） and （18.27±4.22） h; AUC0-72h was （ 199.60±68.89） and （179.55±50.18 ） ng·h·mL-1. The bioavaiability of the bambuterol orally disintegrating tablet were （ 107.4±16.9） % for bambuterol and （ 110.9±18.6） % for terbutalin. Conclusion： Domestic and imported bambuterol formulations are bioequivalent.