塞克硝唑阴道泡腾片人体药代动力学研究

Study of pharmacokinetics of secnidazole vagina effervescent tablets in healthy volunteers

目的:研究塞克硝唑阴道泡腾片人体内的药代动力学特征。方法:单次给药分别应用250、500、750 mg,多次给药应用500 mg,连用7 d,采用HPLC测定血浆中塞克硝唑的浓度。用DAS软件计算其药代动力学参数。结果:健康已婚女性受试者单次使用塞克硝唑阴道泡腾片250、5007、50 mg后的T1/2β分别为18.84、15.25、21.86 h,与文献报道基本一致;Tmax分别为12.22、14.00、18.00 h,Cmax分别为3.58、5.42、8.00 mg.L-1,AUC分别为103.52、190.992、96.92 mg.h-1.L-1,与口服制剂相比,吸收较慢,峰浓度较低,吸收量较少,提示本药全身作用较小,不良反应也较少,局部残留较多有利于发挥治疗作用。多次使用塞克硝唑500 mg后的T1/2β=22.74 h、Cmax=14.30 mg.L-1、Tmax=1 1.60 h、AUC=520.14 mg.h-1.L-1,Cmax和AUC与单次给药相比明显增大,说明该药因半衰期较长,长期用药有一定的蓄积,多次连续用药应引起注意。结论:本试验提供了塞克硝唑阴道泡腾片体内血药浓度的HPLC测定方法及药动学参数,为其临床应用和合理用药提供了参考和依据。

AIM： To study the phannacokinetics of secnidazole vagina effervescent tablets in healthy volunteers. METHODS： 250, 500 and 750 mg secnidazole vagina effervescent tablets were used in single-dose groups; 500 mg seenidazole vagina effervescent tablets were used for 7 days in multi-dose group. The concentrations of secnidazole in plasma were determined by HPLC. The parameters of pharmacokinetics were calculated by DAS software. RESULTS AND CONCLUSION： The pharmacokinetic parameters after administration of a single dose of secnidazole vagina effervescent tablets （250, 500, 750 mg） in health married female volunteers were as follows： Tlao were 18.84, 15.25, and 21.86 h, in accordance with the literatures; Tmax were 12.22, 14.00, and 18.00 h; Cmax were 3.58, 5.42, and 8.00 mg·L^-1; AUC were 103.52,190.99, and 296.92 mg·h^-1 ·L^-1 ,respectively. The absorption of secnidazole vagina effervescent tablets was slower and lower than oral tablets. The systemic actions and adverse reactions were fewer and rudimental concentrations were higher so as to show more local actions. The pharmacokinetic parameters after administration of multi doses of secnidazole vagina effervescent tablets （500 mg） were as follows： T1/2β = 22.74 h, Cmax= 14.30 mg·L^-1, Tmax = 11.60 h, and AUC = 520.14 mg· h^- 1· L^- 1. Cmax and AUC were higher than the results of a single dose. These showed that the drug can cumulate after a long-time administration because of its long half-life and required more caution.