中国成年健康受试者单次口服胶体果胶铋与枸橼酸铋钾的药代动力学研究

Pharmacokinetics study of colloidal bismuth pectin and bismuth potassium citrate after single oral administration in Chinese adult healthy subjects

目的研究健康受试者空腹单次口服胶体果胶铋胶囊(受试制剂T1)、胶体果胶铋颗粒(受试制剂T2)和枸橼酸铋钾片(参比制剂R1)、枸橼酸铋钾颗粒(参比制剂R2)的药代动力学特征及评价其安全性。方法本研究采用随机、开放、四制剂组、平行设计,入选48例受试者,随机分为A、B、C、D组,每组12人,男女各半,A、B、C、D组受试者分别单次空腹服用枸橼酸铋钾片240 mg(以Bi_(2)O_(3)计)、枸橼酸铋钾颗粒2.0 g(含铋220 mg)、胶体果胶铋颗粒2包[每包含胶体果胶铋(以铋计)0.15 g]和胶体果胶铋胶囊6粒[每粒含胶体果胶铋(以铋计)50 mg]。用电感耦合等离子体质谱(ICP-MS)法对健康人血浆中铋元素浓度进行检测,计算药代动力学参数,评价受试制剂胶体果胶铋颗粒、胶体果胶铋胶囊分别与参比制剂枸橼酸铋钾片、枸橼酸铋钾颗粒的AUC_(0-t),AUC_(0-∞)和C_(max)差异,并评价其安全性。结果单剂量空腹给药后铋制剂的主要药代动力学参数如下:C、D、A、B组的C_(max)分别(1.79±0.98),(0.96±0.38),(111.54±98.78),(6.40±2.50)ng·mL^(-1),AUC_(0-t)分别为(15.46±9.92),(12.02±7.60),(240.70±191.08),(28.62±10.41)ng·h·mL^(-1),AUC_(0-∞)分别为(19.27±11.55),(41.10±66.72),(253.39±199.52),(45.11±31.30)ng·h·mL^(-1)。受试制剂的AUC_(0-t)、AUC_(0-∞)和C_(max)不高于参比制剂。结论健康受试者单次口服胶体果胶铋颗粒、胶体果胶铋胶囊的人体铋吸收低于枸橼酸铋钾片和枸橼酸铋钾颗粒,具有良好的安全性。

Objective To study the pharmacokinetic characteristics of colloidal bismuth pectin capsules(T1),colloidal bismuth pectin granules(T2),and bismuth potassium citrate tablets(R1),bismuth potassium citrate granules(R2)and its safety.Methods The study adopted a randomized,open,four-agent group,and parallel design.48 subjects were enrolled.They were randomly divided into four groups,A,B,C,and D,with 12 subjects in each group,half male and female,and A,B,C,D groups of subjects were respectively given bismuth potassium citrate tablets 240 mg(calculated as Bi_(2)O_(3)),bismuth potassium citrate granules(2.0 g per bag:containing bismuth 220 mg),colloidal bismuth pectin granules[each containing colloidal pectin bismuth(calculated as bismuth)0.15 g]and colloidal pectin bismuth capsules[each capsule contains colloidal pectin bismuth(calculated as bismuth)50 mg].Inductively coupled plasma mass spectrometry(ICP-MS)was used to detect the concentration of bismuth in the plasma of healthy people,pharmacokinetic parameters were calculated,and the AUC_(0-t),AUC_(0-∞) and Cmax of the test preparations colloidal bismuth pectin particles and colloidal bismuth pectin capsules were compared with the preparation of bismuth potassium citrate tablets and bismuth potassium citrate granules,and the safety was evaluated.Results The main pharmacokinetic parameters of bismuth preparations after single-dose fasting administration are as follows.Cmaxof C,D,A,B groups were(1.79±0.98),(0.96±0.38),(111.54±98.78),(6.40±2.50)ng·mL^(-1),AUC_(0-t) were(15.46±9.92),(12.02±7.60),(240.70±191.08),(28.62±10.41)ng·h·mL^(-1),AUC_(0-∞) were(19.27±11.55),(41.10±66.72),(253.39±199.52),(45.11±31.30)ng·h·mL^(-1),respectively.The AUC_(0-t),AUC_(0-∞) and Cmax of the test formulation were not higher than the reference formulation.Conclusion The human bismuth absorption of colloidal bismuth pectin granules and colloidal bismuth pectin capsules in healthy subjects is lower than that of bismuth potassium citrate tablets and bismuth potassium citrate granules,and they have good safety.