Brimhall Darin B, Chen Yu-Luan, Lee Sarah, Yoshida Kazumasa, Ufer Mike
PPD Incorporation-Thermo Fisher Scientific, Waltham, Massachusetts, USA.
Sumitomo Pharma America, Marlborough, Massachusetts, USA.
Pharmacol Res Perspect. 2025 Feb;13(1):e70067. doi: 10.1002/prp2.70067.
Relugolix is an oral gonadotropin-releasing hormone receptor antagonist that suppresses sex steroid hormones and is approved as monotherapy for prostate cancer and as a fixed-dose combination with estradiol/norethindrone for the treatment of endometriosis and uterine fibroids. The aim of this postmarketing study was to determine the pharmacokinetics and quantify the amount of relugolix excreted into breast milk of healthy lactating women. Following a single, oral dose of 40 mg relugolix, breast milk was sampled over 120 h. Pharmacokinetic parameters were determined, including the cumulative amount of relugolix excreted into breast milk to derive the total infant dose. The safety and tolerability of relugolix were also assessed. Eight healthy lactating women were enrolled and completed the study per protocol. Relugolix was safe and well tolerated based on adverse events and other safety data. It was excreted into breast milk with a median time to peak concentration (t) of 5.81 h and a geometric mean peak concentration (C) of 15.7 ng/mL, similar to corresponding plasma data from previous clinical studies. The mean cumulative amount of relugolix excreted was 0.0051 mg over 24 h and 0.0067 mg over 120 h, corresponding to 0.0128% and 0.0167% of the maternal dose, respectively. The body weight-adjusted relative daily infant dose of approximately 0.25% suggests a 400-fold lower newborn than maternal relugolix exposure. Relevant effects of relugolix on the breastfed child appear unlikely given its limited excretion into breast milk of lactating women but cannot be fully excluded in the absence of infant safety data.
瑞卢戈利是一种口服促性腺激素释放激素受体拮抗剂，可抑制性甾体激素，已被批准作为前列腺癌的单一疗法，以及与雌二醇/炔诺酮的固定剂量组合用于治疗子宫内膜异位症和子宫肌瘤。这项上市后研究的目的是确定健康哺乳期妇女的药代动力学，并量化瑞卢戈利排泄到母乳中的量。单次口服40毫克瑞卢戈利后，在120小时内采集母乳样本。测定药代动力学参数，包括排泄到母乳中的瑞卢戈利累积量，以得出婴儿的总剂量。还评估了瑞卢戈利的安全性和耐受性。八名健康哺乳期妇女按方案入组并完成了研究。根据不良事件和其他安全数据，瑞卢戈利是安全且耐受性良好的。它排泄到母乳中，中位达峰时间（t）为5.81小时，几何平均峰浓度（C）为15.7纳克/毫升，与先前临床研究的相应血浆数据相似。瑞卢戈利排泄的平均累积量在24小时内为0.0051毫克，在120小时内为0.0067毫克，分别相当于母体剂量的0.0128%和0.0167%。体重调整后的相对每日婴儿剂量约为0.25%，表明新生儿接触瑞卢戈利的量比母体低400倍。鉴于瑞卢戈利在哺乳期妇女母乳中的排泄量有限，其对母乳喂养儿童的相关影响似乎不太可能，但在缺乏婴儿安全数据的情况下不能完全排除。
