20min采血药动学方法评价沙丁胺醇气雾剂的生物等效性

Bioequivalent evaluation of two salbutamol aerosols by pharmacokinetic method sampling over 20 minutes

目的 以 2 0min采血药动学方法评价两种沙丁胺醇气雾剂在健康受试者的生物等效性。方法 采用随机分组、自身对照设计 ,18名男性健康志愿受试者分别吸入两种沙丁胺醇气雾剂 12 0 0 μg ,采集 2 0min内血浆样本 ,采用HPLC测定血浆药物浓度 ,用非房室模型计算AUC0～ 2 0min,cmax,tmax等参数 ,对AUC0～ 2 0min和cmax进行方差分析和双向单侧t检验 ,评价两种制剂的生物等效性。结果 参比制剂和试验制剂的AUC0～ 2 0min分别为 (0 .71± 0 .32 )和 (0 .4 6± 0 .2 7)ng·h·mL-1,cmax分别为(2 .97± 1.38)和 (1.91± 1.18)ng·mL-1,tmax分别为 (0 .2 1± 0 .0 7)和 (0 .19± 0 .0 9)h。试验沙丁胺醇气雾剂的相对生物利用度为 5 8.4 %。双向单侧t检验结果分别为T(H) AUC=6 .79,T(L) AUC=- 2 .81;T(H) cmax=7.16 ,T(L) cmax=- 1.32。结论 试验与参比沙丁胺醇气雾剂生物不等效。

OBJECTIVE: To evaluate the bioequivalence of two salbutamol aerosols in healthy subjects using a special pharmacokinetic method. METHODS: A randomized, two - way crossover, open design was adopted. 18 healthy male subjects were enrolled. Single doses of 1200 μg salbutamol as generic salbutamol aerosol (12 × 100 μg) and Ventolin (12 × 100 μg) were administered over 6 min. Mouth rinsing was performed after every inhalation. Blood samples were taken before administration and at 5, 10, 15 and 20 min after inhalation. The concentrations of salbutamol in plasma were determined by HPLC assay. The AUC0∼20 min and cmax were evaluated by analysis of variance and two one-sided t-test. RESULTS: The parameters of the reference and test salbutamol aerosols were AUC0∼20 min (0.71±0.32) and (0.46±0.27) ng&middoth&middotmL-1, cmax(2.97±1.38) and (1.91±1.18) ng&middotmL-1, tmax(0.21± 0.07) and (0.19±0.09) h, respectively. The relative bioavailability of the test salbutamol aerosol was 58.4 %. The results of two one-sided t test were as following: T(H)AUC = 6.79, T(L)AUC = -2.81, T(H)cmax = 7.16, T(L)cmax = -1.32. CONCLUSION: The two formulations were not bioequivalent.