van der Merwe R, Lugan I, Lecuelle H, Papasouliotis O, Buraglio M
Bourn Hall Clinic, Cambridge, UK.
Curr Med Res Opin. 2004 Mar;20(3):397-402. doi: 10.1185/030079904125003044.
To compare the bioavailability and tolerability of liquid and freeze-dried formulations of recombinant human chorionic gonadotrophin (r-hCG).
In an open-label, randomised, single-centre, Phase I study, healthy adult volunteers (18-50 years of age) received single injections of r-hCG 250 microg from reconstituted freeze-dried (1.0 mL of 250 microg/mL) and liquid (0.5 mL of 250 microg/0.5 mL) formulations in random order, separated by a 10-day wash-out period. Pharmacokinetics (C(max), AUC, AUC(last), t(max)) and local and systemic tolerability were assessed.
Pharmacokinetic properties of the two formulations were very similar, with mean C(max) 125 mIU/mL (liquid formulation) vs 129 mIU/mL (freeze-dried formulation), mean AUC 10,350 mIU.h/mL vs 10,480 mIU(.)h/mL, mean AUC(last) 10,050 mIU.h/mL vs 10,210 mIU.h/mL, and median t(max) 20 vs 24h. The 90% confidence intervals of the ratios of the treatment means for C(max), AUC and AUC(last) all fell within the pre-defined FDA acceptance range of 0.8-1.25, demonstrating the bioequivalence of the two formulations. Both formulations were equally well tolerated; the most frequent adverse events were headache and nausea.
The liquid formulation of r-hCG was shown to be bioequivalent to the freeze-dried formulation, with no clinically significant differences in tolerability. The liquid formulation of r-hCG can be expected to provide the same efficacy and tolerability as the freeze-dried formulation when used to trigger final follicular maturation in women undergoing therapies for assisted reproduction, together with a greater convenience of use.
比较重组人绒毛膜促性腺激素（r-hCG）液体剂型和冻干剂型的生物利用度及耐受性。
在一项开放标签、随机、单中心的I期研究中，健康成年志愿者（18至50岁）以随机顺序接受单次注射250微克重组人绒毛膜促性腺激素，分别来自复溶后的冻干剂型（1.0毫升，250微克/毫升）和液体剂型（0.5毫升，250微克/0.5毫升），两次注射间隔10天的洗脱期。评估了药代动力学参数（Cmax、AUC、AUC（末次）、tmax）以及局部和全身耐受性。
两种剂型的药代动力学特性非常相似，液体剂型的平均Cmax为125毫国际单位/毫升，冻干剂型为129毫国际单位/毫升；平均AUC分别为10350毫国际单位·小时/毫升和10480毫国际单位·小时/毫升；平均AUC（末次）分别为10050毫国际单位·小时/毫升和10210毫国际单位·小时/毫升；中位tmax分别为20小时和24小时。Cmax、AUC和AUC（末次）治疗均值比值的90%置信区间均落在FDA预先定义的0.8至1.25接受范围内，表明两种剂型生物等效。两种剂型的耐受性相当；最常见的不良事件为头痛和恶心。
r-hCG液体剂型与冻干剂型生物等效，耐受性无临床显著差异。在辅助生殖治疗中用于促使女性最终卵泡成熟时，r-hCG液体剂型有望与冻干剂型具有相同的疗效和耐受性，且使用更方便。
