重组人促卵泡激素在健康女性受试者中单次给药的生物等效性研究

Bioethicity of recombinant human follicle-stimulating hormone in a single administration in healthy female subjects

目的评估2种重组人促卵泡激素注射液在健康女性受试者中的生物等效性和安全性。方法采用随机、开放、两周期、两交叉设计,32例健康女性受试者单次注射重组人促卵泡激素受试制剂或参比制剂225 U,用验证的MSD法测定健康受试者给药前后血清样品重组人促卵泡激素的血药浓度,用Phoenix WinNonlin 7.0软件计算药代动力学参数。结果皮下注射受试制剂和参比制剂后主要药代动力学参数:C_(max)分别为(6.85±2.04)和(7.17±2.26)mU·mL^(-1);AUC_(0-t)分别为(500.20±144.85)和(455.30±138.75)h·U·mL^(-1);AUC_(0-∞)分别为(525.50±102.33)和(458.00±151.58)h·U·mL^(-1)。受试制剂与参比制剂C_(max)和AUC_(0-t)几何均值比的90%置信区间分别为89.08%~102.91%以及101.46%~119.83%,均落在80%~125%。试验过程中,无严重不良事件和非预期不良事件发生。结论2种重组人促卵泡激素在健康女性受试者中具有生物等效性且安全性良好。

Objective To evaluate the bioequivalence and safety of two recombinant human follicle-stimulating hormone injections in healthy female subjects.Methods Thirty-two healthy female subjects were given a single dose of recombinant human follicle-stimulating hormone test or reference preparation 225 U by randomized,open,two cycle,two cross design.The serum concentrations of recombinant human follicle-stimulating hormone in healthy subjects before and after administration were measured by validated MSD method,and pharmacokinetics parameters were calculated with Phoenix WinNonlin 7.0 software.Results The main pharmacokinetics parameters after single subcutaneous injection were as follows:C_(max) were(6.85±2.04)and(7.17±2.26)mU·mL^(-1);AUC_(0-t) were(500.20±144.85)and(455.30±138.75)h·U·mL^(-1);AUC_(0-∞)were(525.50±102.33)and(458.00±151.58)h·U·mL^(-1).The 90% confidence intervals of the geometric mean ratios of C_(max) and AUC_(0-t) were 89.08%-102.91% and 101.46%-119.83%,respectively,which were in the range of 80%-125%.During the trial,no serious adverse event or suspected unexpected serious adverse reaction occurred.Conclusion The recombinant human follicle-stimulating hormone injection has good bioequivalence and safety in healthy female subjects.