塞克硝唑阴道泡腾片Ⅰ期临床耐受性研究

PhaseⅠclinical tolerability of secnidazole vagina effervescent tablets

目的:评价塞克硝唑阴道泡腾片在健康已婚女性中单次和多次给药的安全性、耐受性。方法:按GCP要求设计试验方案。单次给药耐受性试验中将20例受试者按体重分层随机分至125,250,500, 750 mg共4个剂量组中,每组分别为4,6,6,4例,从最低剂量组开始给药。根据单次给药耐受性试验结果开始多次给药耐受性试验。多次给药耐受性试验入选12例受试者,按体重分层随机分为2组,应用不同剂量塞克硝唑阴道泡腾片,每曰1次,连用7 d。结果:多次给药耐受性试验中2组给药剂量为250, 500 mg·d^(-1)。单次给药耐受性试验中,各组受试者入选时各项指标均正常,条件均衡具较好可比性。试验中无不良反应发生,也未见其他有临床意义的改变。多次给药耐受性试验中亦未见严重不良反应,仅500 mg·d^(-1)组有3例出现轻度外阴烧灼感,0．5 h内自行消失。结论:单次应用塞克硝唑阴道泡腾片,最大剂量至750 mg,多次用药250 mg·d^(-1)比较安全、耐受性较好。

AIM： To evaluate the safety and tolerability of single-dose and multi-dose administration of secnidazole vagina effervescent tablets in healthy married female volunteers. METHODS： The protocol was designed according to the Good Clinical Practice （GCP）. Twenty healthy volunteers were randomly divided into 4 dosage groups： 125, 250, 500 and 750 mg, with 4, 6, 6, 4 volunteers in each. The tablets were administered from the lowest dosage. The experimentations of multi-dose were carried on according to the results of single-dose. Twelve healthy volunteers were randomly divided into 2 dosage groups with 6 volunteers in each, administering with different dosage once a day for 7 d. RESULTS： The dosages in experimentations of multidose were 250 and 500 mg·d^-1. The volunteers in each group possessed good proportional equivalence for comparison before administration of secnidazole vagina effervescent tablets. After single-dose administration of secnidazole vagina effervescent tablets, most clinical symptoms, vital signs and laboratory tests were normal without significant clinical changes or adverse drug reactions （ADRs）. No severe ADRs were observed after multi-dose administration of secnidazole vagina effervescent tablets, but only 3 volunteers with slight vulval burn feeling in 500 mg·d^-1 group and recovered after 0.5 h. CONCLUSION： Single-dose up to the maximum dosage of 750 mg and multi-dose of 250 mg·d^-1 secnidazole vagina effervescent tablets are safe and tolerable.