Department of Pharmacology, Merck, Sharpe and Dohme MSD, 5340 BH Oss, The Netherlands.
Eur J Pharmacol. 2011 Jan 25;651(1-3):227-33. doi: 10.1016/j.ejphar.2010.10.078. Epub 2010 Nov 27.
Corifollitropin alfa (Elonva®, MSD, previously N.V. Organon or Schering-Plough Oss, The Netherlands) is a newly developed sustained follicle stimulant composed of the α subunit of human follicle-stimulating hormone (FSH) and a hybrid β subunit formed by fusion of the human chorionic gonadotropin β subunit carboxy terminal peptide with the β subunit of human FSH. Binding characteristics of corifollitropin alfa at the rat FSH receptor and transactivation properties at the rat FSH receptor, human luteinizing hormone (LH) receptor, and human thyroid-stimulating hormone receptor (TSH receptor) were assessed in vitro. Bioactivity of corifollitropin alfa in rats was also assessed. Serum corifollitropin alfa levels in rats and dogs were used to derive the main pharmacokinetic parameters of corifollitropin alfa. Binding and transactivation profile of corifollitropin alfa to rat FSH receptor was specific and comparable to that of recombinant human FSH, with no intrinsic TSH receptor or LH receptor activation. From pharmacokinetic studies, circulating half-life of corifollitropin alfa was calculated to be 17.3h in rats and 46.9h in dogs, 1.5- to 2-fold longer than recombinant FSH. Corifollitropin alfa demonstrated a 2- to 4-fold increase in bioactivity (ovarian weight, serum estradiol and progesterone, ovulated ova) over recombinant FSH across all in vivo parameters assessed. These data demonstrate that corifollitropin alfa is a specific ligand with high affinity for FSH receptor, lacking intrinsic activity for LH receptor and TSH receptor. By virtue of its increased in vivo half-life, corifollitropin alfa can be a valuable alternative to FSH by acting as a sustained follicle stimulant.
科尔福利托林阿尔法（Elonva®，默沙东，前身为 N.V.Organon 或 Schering-Plough Oss，荷兰）是一种新开发的持续卵泡刺激素，由人卵泡刺激素（FSH）的α亚基和通过人绒毛膜促性腺激素β亚基羧基末端肽与人 FSH 的β亚基融合形成的杂交β亚基组成。在体外评估了科尔福利托林阿尔法在大鼠 FSH 受体上的结合特性和在大鼠 FSH 受体、人促黄体激素（LH）受体和人促甲状腺激素受体（TSH 受体）上的转激活特性。还评估了科尔福利托林阿尔法在大鼠中的生物活性。使用大鼠和狗的血清科尔福利托林阿尔法水平来推导出科尔福利托林阿尔法的主要药代动力学参数。科尔福利托林阿尔法与大鼠 FSH 受体的结合和转激活谱是特异性的，与重组人 FSH 相当，没有内在的 TSH 受体或 LH 受体激活。从药代动力学研究中，计算出科尔福利托林阿尔法在大鼠中的循环半衰期为 17.3 小时，在狗中为 46.9 小时，比重组 FSH 长 1.5 至 2 倍。科尔福利托林阿尔法在所有评估的体内参数中表现出比重组 FSH 高 2 至 4 倍的生物活性（卵巢重量、血清雌二醇和孕酮、排出的卵子）增加。这些数据表明，科尔福利托林阿尔法是一种具有高亲和力的 FSH 受体特异性配体，缺乏 LH 受体和 TSH 受体的内在活性。由于其体内半衰期增加，科尔福利托林阿尔法可以作为一种持续的卵泡刺激素，成为 FSH 的一种有价值的替代品。
