氯沙坦钾片人体生物等效性研究

目的:研究2种氯沙坦钾片的人体生物等效性。方法:20名健康受试者按随机双交叉设计,单剂量口服氯沙坦钾片受试制剂与参比制剂100mg后,采用液-质联用(LC-MS)法测定氯沙坦及其代谢物EXP3174的血药浓度,计算药动学参数并进行生物等效性评价。结果:受试制剂与参比制剂氯沙坦的药动学参数分别为Cma(x534.230±238.642)、(520.020±226.800)ng.mL-1,tmax(1.401±0.946)、(1.334±0.750)h,AUC0～36(871.177±232.315)、(773.030±252.209)ng.h.mL-1,AUC0～∞(881.005±235.070)、(781.131±252.455)ng.h.mL-1;其代谢物EXP3174的药动学参数分别为Cma(x1294.000±387.815)、(1140.900±317.615)ng.mL-1,tma(x2.667±1.144)、(2.734±1.162)h,AUC0～36(6267.905±1350.300)、(5719.411±1127.725)ng.h.mL-1,AUC0～∞(6316.605±1343.048)、(5755.335±1138.358)ng.h.mL-1。受试制剂相对生物利用度为(116.6±24.3)%。结论:氯沙坦钾片受试制剂与参比制剂生物等效。

Study on Bioavailability of Losartan Potassium Tablets

OBJECTIVE：To study the bioequivalence of 2 kinds of Losartan potassium tablets in healthy volunteers. METHODS： A single oral dose of test tablet 100 mg and reference tablet 100 mg were given to 20 healthy volunteers in randomized crossover study. The plasma concentrations of losartan and its metabolite EXP3174 were determined by LC-MS. The pharmacokinetic parameters were calculated and bioequivalence of 2 kinds of tablets was evaluated. RESULTS： Main pharmacokinetic parameters of Losartan of test tablets vs. reference tablets were as follows： Cmax（534.230±238.642） ng·mL-1 vs.（520.020±226.800） ng·mL-1; tmax（1.401±0.946）h vs.（1.334±0.750）h; AUC0～36（871.177±232.315） ng·h·mL-1 vs. （773.030±252.209） ng·h·mL-1; pharmacokinetic parameters of metabolite EXP3174 of test tablets vs. reference tablets were as follows： Cmax （1 294.000±387.815） ng·mL-1 vs.（1 140.900±317.615）ng·mL-1;tmax（2.667±1.144）h vs.（2.734±1.162）h;AUC0～36（6 267.905±1 350.300）ng·h·mL-1 vs.（5 719.411±1 127.725） ng·h·mL-1; AUC0～∞（6 316.605±1 343.048）ng·h·mL-1 vs. （5 755.335±1 138.358） ng·h·mL-1. The relative bioavailability of test tablet was （116.6±24.3）%. CONCLUSION： 2 kinds of Losartan potassium tablets are bioequivalent.