呋塞米片在中国健康受试者的生物等效性研究

Bioequivalence study of furosemide tablets in Chinese healthy subjects

目的评价呋塞米片在人体空腹状态下相对生物利用度及生物等效性。方法 20名健康男性受试者按随机交叉、自身对照、两周期试验设计,单次空腹口服呋塞米片受试制剂或参比制剂40 mg。用高效液相色谱-串联质谱法测定血浆中呋塞米浓度,用DAS 3.2.8软件计算药代动力学参数。结果 2位受试者因个人事务未能完成最终试验,视为脱落病例,未纳入数据统计。18名受试者单次口服呋塞米片受试制剂或参比制剂40 mg后的主要药代动力学参数:AUC0-12 h分别为(3430.36±1016.96),(3669.43±1158.51)ng·m L^(-1)·h;AUC0-∞分别为(3551.03±1025.10),(3788.12±1162.49)ng·m L^(-1)·h;tmax分别为(1.86±0.89),(1.44±0.89)h;Cmax分别为(1219.80±353.59),(1359.65±436.36)ng·m L^(-1);t1/2分别为(3.02±0.69),(3.00±1.50)h,相对生物利用度为(94.59±11.71)%。结论呋塞米片受试制剂和参比制剂具有生物等效性。

Objective To evaluate the bioavailability and bioequivalence of two 40 mg oral furosemide tablets in Chinese healthy male subjects.Methods A single dose,randomized,two-period and crossover study was conducted in subjects under fasting conditions.Each subject received test or reference tablets.The plasma concentrations of furosemide were determined by HPLC-MS/MS.DAS 3.2.8 was used for pharmacokinetic parameters calculation.Results Two subjects didn ＇t finish the experiment due to personal affairs,so they were excluded and considered as drop-outs.The main pharmacokinetic parameters of the remaining 18 subjects were as follows：AUC0-12 hwere（3430.36 ± 1016.96）,（3669.43 ± 1158.51） ng·m L^（-1）·h;AUC0-∞were（3551.03 ± 1025.10）,（3788.12 ± 1162.49） ng·m L^（-1）·h;tmax were（1.86 ± 0.89）,（1.44 ± 0.89） h;Cmaxwere（1219.80 ± 353.59）,（1359.65 ± 436.36） ng · m L-1;t1/2were（3.02 ± 0.69）,（3.00 ± 1.50） h.The relative bioavailability was（94.59 ± 11.71） %.Conclusion Results show that the test and reference formulation are bioequivalent.