螺内酯片在健康人体内药代动力学及生物等效性

Bioequivalence and pharmacokinetics of spironolactone tablets in healthy volunteers

目的研究螺内酯片(利尿药,抗高血压药)在健康人体内的相对生物利用度,并进行生物等效性评价。方法采用随机交叉自身对照试验设计,18名健康男性受试者分别单剂量口服螺内酯受试制剂或参比制剂25 mg后,取静脉血,采用HPLC-MS法测定其活性代谢产物坎利酮的血浆浓度,计算主要药代动力学参数。以方差分析进行均数的差别检验,以双单侧t检验进行生物等效性判定。结果受试者分别口服受试制剂和参比制剂后,坎利酮的主要药代动力学参数如下:AUC0→72分别为(684.8±184.4)、(682.1±212.7)μg.h.L-1,AUC0→∞分别为(803.8±249.6)、(774.3±259.3)μg.h.L-1,tmax分别为(2.1±0.3)、(1.9±0.4)h,Cmax分别为(51.3±12.4)、(54.1±12.9)μg.L-1,t1/2分别为(25.0±9.2)、(22.1±6.0)h。受试制剂对参比制剂的相对生物利用度为(102.2±19.0)%。结论受试制剂与参比制剂为生物等效制剂。

Objective To study the pharmacokinetics and bioavailability of spironolactone tablets in healthy volunteers. Methods A cross-over, randomized study was performed in 18 healthy male volunteers receiving a single oral dose of 25 mg of the tested or the referenced spironolactone tablets. A sensitive and specific HPLC-MS method was developed to quantitate the concentrations of canrenone in plasma, which is one of the major active metabolites of spironolactone. The pharmacokinetic parameters were analysed by two one-side t test to determine the bioequivalence of the two preparations. Results The main pharmacokinetic parameters of the tested and the referenced preparations were as follows： AUC0→72 were （684.8 ± 184. 4）μg.h.L^-1and （682. 1 ±212.7） μg.h.L^-1, AUC0→∞ were （ 803.8 ± 249.6） μg.h.L^ -1 and （774.3 ± 259.3 ） μg.h.L^-1,tmax were （2. 1 ±0.3）h and （1.9 ±0.4）h,Cmax were （51.3 ± 12.4） μg.L^-1 and （54. 1 ±12.9）μg.L^-1, t1/2 were （25.0±9.2） h and （22. 1 ± 6. 0）h. The relative bioavailability of canrenone was （ 102.2 ± 19.0）%. Conclusion The tested and the referenced preparations are bioequivalent.