The goals of this clinical trial are to investigate the effect of the estetrol (E4)-drospirenone combined oral contraceptive (COC) pill on flow-mediated dilatation (FMD) of the brachial artery and pulse wave velocity (PWV), in comparison to the ethinylestradiol (EE)-levonorgestrel COC pill, and to compare their respective effects on blood pressure, chronic inflammatory markers, as well as glycaemic and lipid indices.
The main questions it aims to answer are:
Does E4-drospirenone COC have significantly smaller effects then EE-levonorgestrel COC on FMD, PWV, blood pressure, chronic inflammatory markers, as well as glycemic and lipid indices.
Researchers will compare E4-drospirenone to EE-levonorgestrel to see if the former has lower arterial vascular and metabolic risks.
Participants will:
* be randomised to take E4-drospirenone or EE-levonorgestrel COC pill according to product insert;
* visit the clinic at baseline and 6 and 12 months post-recruitment for checkups and tests

开始日期2026-07-01

申办/合作机构

香港大学

[+1]

JPRN-jRCT2031250241

/ Recruiting临床3期

A Multi-center, Randomized, Double-Blind, Placebo-Controlled, Parallel-group design study to evaluate the efficacy and safety after cyclic dose of FSN-013 (E4/DRSP) in Japanese patients with Endometriosis

开始日期2025-05-01

申办/合作机构

Fuji Pharma Co., Ltd.

TCTR20250319011

/ Completed临床4期IIT

The impact of Estetrol/Drospirenone versus Ethinyl Estradiol/Drospirenone on testosterone level and clinical outcomes in women with polycystic ovary syndrome (PCOS): A randomized controlled non-inferiority trial

开始日期2025-03-27

申办/合作机构-

100 项与雌四醇/屈螺酮相关的临床结果

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100 项与雌四醇/屈螺酮相关的转化医学

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100 项与雌四醇/屈螺酮相关的专利（医药）

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项与雌四醇/屈螺酮相关的文献（医药）

2026-06-01·JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH

Cerebral Venous Sinus Thrombosis Occurring During Estetrol/Drospirenone Combined Oral Contraceptive Use in a Woman With Multiple Thrombotic Risk Factors: A Case Report

Article

作者: Ogishima, Daiki ; Kasahara, Hanako ; Ito, Yosuke ; Maruyama, Yojiro ; Nakahara, Mariko ; Fuse, Atsuhito

ABSTRACT:

Estetrol/drospirenone (E4/DRSP) is a combined oral contraceptive noted for its minimal hemostatic impact compared to ethinyl estradiol‐based preparations. However, real‐world thrombotic risk data in patients with significant comorbidities remain limited. A woman in her early 40s with adenomyosis and menorrhagia was prescribed E4/DRSP. Six weeks later, she developed acute left upper extremity weakness; imaging confirmed superior sagittal sinus thrombosis. She had severe iron deficiency anemia (hemoglobin 6.4 g/dL). Multiple overlapping risk factors—including severe iron deficiency anemia with reactive thrombocytosis, adenomyosis, obesity, hypertension, and age over 40—likely contributed synergistically, and the independent contribution of E4/DRSP cannot be determined. She was treated with anticoagulation and transitioned to relugolix for adenomyosis management. Although E4/DRSP has a favorable coagulation profile, thrombotic risk persists in women with adenomyosis and severe anemia. Pre‐prescription assessment including correction of anemia and consideration of estrogen‐free alternatives is warranted.

2025-04-01·FERTILITY AND STERILITY

Efficacy and safety of estetrol (15 mg)/drospirenone (3 mg) combination in a cyclic regimen for the treatment of primary and secondary dysmenorrhea: a multicenter, placebo-controlled, double-blind, randomized study

Article

作者: Mochiyama, Takayuki ; Osuga, Yutaka ; Hirakawa, Akihiro ; Takayanagi, Toshiaki ; Hirayama, Masashi ; Nogami, Masayoshi ; Kobayashi, Takao ; Harada, Tasuku ; Tayzar, Kyaw ; Foidart, Jean-Michel

OBJECTIVE:

To evaluate the efficacy and safety of the estetrol (E4) (15 mg)/drospirenone (DRSP) (3 mg) combination in a cyclic regimen in Japanese women with primary and secondary dysmenorrhea.

DESIGN:

A 16-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, followed by a 36-week, open-label, extension study.

SUBJECTS:

A total of 162 Japanese women with primary and secondary dysmenorrhea.

INTERVENTION:

Participants were randomly allocated to either the E4/DRSP group or the placebo group. In the E4/DRSP group, participants orally received one tablet containing E4 (15 mg) and DRSP (3 mg daily) for 24 days, followed by a placebo tablet for 4 days, constituting one cycle. The placebo group was given one placebo tablet daily for 28 days. After 16 weeks, participants in the placebo group were switched to receive E4/DRSP for 36 weeks.

MAIN OUTCOME MEASURES:

Absolute change in the most severe total dysmenorrhea score from baseline to the end of the 16-week double-blinded period.

RESULTS:

Estetrol/drospirenone reduced the most severe total dysmenorrhea score by 2.3 points from baseline at week 16. The between-group difference was significant (-1.4, two-sided 95% confidence interval, -1.8 to -1.0), showing superiority to placebo. The responder rate, the proportion of participants who achieved a ≥2.0-point reduction in the most severe total dysmenorrhea score from baseline, was 64.3% in the E4/DRSP group, significantly higher than in the placebo group, 28.4%. In the E4/DRSP group, visual analogue scale scores for pelvic pain and dysmenorrhea symptoms during the menstrual bleeding periods were decreased by 44.2 and 42.3 mm, respectively, from baseline at week 16, significantly more than in the placebo group. Objective gynecological examinations suggested amelioration of pelvic tenderness, uterine mobility, and cul-de sac induration in the E4/DRSP group. Estetrol/drospirenone improved the quality of life-related questionnaires (interference with daily activities and sleeping) and global impression scores. Intermenstrual bleeding was the primary treatment-emergent adverse event in the E4/DRSP group, similar to combined oral contraceptives. There were no cases of venous thromboembolism and less impact on hemostasis parameters in the E4/DRSP group.

CONCLUSION:

Estetrol/drospirenone is an effective treatment for dysmenorrhea, offering a safe, new treatment option with potentially reduced thromboembolic risk.

CLINICAL TRIAL REGISTRATION NUMBER:

jRCT2011210023.

2024-07-03·EUROPEAN JOURNAL OF CONTRACEPTION AND REPRODUCTIVE HEALTH CARE

Effects of E4/DRSP on self-reported physical and emotional premenstrual and menstrual symptoms: data from the phase 3 clinical trial in Europe and Russia

Article

作者: Foidart, Jean-Michel ; Bouchard, Céline ; Apolikhina, Inna ; Gemzell-Danielsson, Kristina ; Bitzer, Johannes ; Piltonen, Terhi ; Zatik, János ; Weyers, Steven ; Creinin, Mitchell D. ; Suturina, Larisa ; Jost, Maud

PURPOSE:

To describe the effects of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg on physical and emotional premenstrual and menstrual symptoms.

MATERIALS AND METHODS:

We used Menstrual Distress Questionnaire (MDQ) data from a phase-3 trial (NCT02817828) in Europe and Russia with participants (18 - 50 years) using E4/DRSP for up to 13 cycles. We assessed mean changes in MDQ-t-scores from baseline to end of treatment in premenstrual (4 days before most recent flow) and menstrual (most recent flow) scores for 4 MDQ domains in starters and switchers (use of hormonal contraception in prior 3 months) and performed a shift analysis on individual symptoms within each domain.

RESULTS:

Of 1,553 treated participants, 1,398(90.0%), including 531(38%) starters, completed both MDQs. Starters reported improvements for premenstrual Pain (-1.4), Water Retention (-3.3) and Negative Affect (-2.5); and for menstrual Pain (-3.5), Water Retention (-3.4), and Negative Affect (-2.7) (all p < 0.01). For switchers, no changes were significant except an increase in premenstrual (+1.0, p = 0.02) and menstrual (+1.5, p = 0.003) Water Retention. We observed a change in symptom intensity in >40% of participants for Cramps, Backache and Fatigue (domain Pain), Painful or Tender Breast and Swelling (domain Water Retention) and Mood Swings and Irritability (domain Negative Affect).

CONCLUSION:

E4/DRSP starters experienced significant improvements in the domains Pain, Water Retention and Negative Affect particularly benefiting those with more severe baseline symptoms. Switchers showed minimal changes.

项与雌四醇/屈螺酮相关的新闻（医药）

2026-10-14

·gedeonrichter.com

Richter receives FDA Submission Acceptance of New Drug Application for FYLREVY® in the U.S.

Gedeon Richter, a company committed to advancing women’s health, today announces that the U.S. Food and Drug Administration (“FDA”) has accepted for review its New Drug Application (NDA) for FYLREVY®, its innovative, orally administered Estetrol (“E4”)-based oestrogen therapy designed to treat moderate to severe vasomotor symptoms (VMS) due to menopause. The FDA is expected to complete its review by Q3 2027. If approved, FYLREVY® would be the first Menopausal Hormone Therapy containing E4 on the U.S. market. In March 2026, FYLREVY® was already granted a marketing authorization by the European Commission for all member states of the European Economic Area as HRT for oestrogen deficiency symptoms in non-hysterectomised postmenopausal women with at least 12 months since last menses (FYLREVY® 14.2 mg and 18.9 mg) and as HRT for oestrogen deficiency symptoms in hysterectomized postmenopausal women (FYLREVY® 18.9 mg). To date, FYLREVY® is commercialized in Hungary, Czech Republic, Slovakia, Finland and Sweden. Dr. Péter Turek, Head of Women’s Healthcare Business Unit at Richter, commented: “We are very pleased to have received filing acceptance in the U.S., the world's largest pharmaceutical market, for our latest innovation in menopause. Despite the significant burden that postmenopausal symptoms place on millions of women, therapeutic progress in this field has remained limited. This milestone reflects Richter's long-standing commitment to innovation and to address this significant unmet medical need. We continue to explore the best path to bring this therapy to patients in the U.S., as part of our broader ambition to advance women's health worldwide.” About FYLREVY® The orally administered Estetrol-based oestrogen therapy FYLREVY® is designed to treat the broad spectrum of oestrogen deficiency symptoms in postmenopausal women, including VMS. Estetrol (“E4") is a native and selective oestrogen produced by the foetal liver during pregnancy and is synthesized from plant sources for pharmaceutical purposes. Preclinical and clinical data for E4 points to a tissue-specific activity and a more selective pharmacological profile compared to other oestrogens, including a low impact on the liver, hemostasis balance and breast cell proliferation. The efficacy and safety of E4 in alleviating VMS was evaluated in two independent, confirmatory, pivotal phase 3 studies (E4COMFORT I and E4COMFORT II) having enrolled a total of 2576 postmenopausal women in Europe, Russia, United States of America (USA), Canada and Latin America. In addition to its authorization in over 50 countries worldwide as the oestrogen component of a combined oral contraceptive with drospirerone (marketed as DROVELIS® in EU and NEXTSTELLIS ® in the U.S.), E4 is now further expanding its therapeutic reach in the menopause field. About Menopause Menopause is a natural biological process marking the end of a woman's reproductive years, typically occurring between 45 and 55 years old. It is characterized by the cessation of menstruation due to decreased production of oestrogens and progesterone by the ovaries. The most frequently reported symptoms include vasomotor symptoms (VMS, which include hot flushes and night sweats), vulvo-vaginal atrophy (VVA), sleep disturbances, impaired bone health, physical changes (amongst which musculoskeletal symptoms, weight gain, thinning hair and dry skin), mood changes (including increased irritability, anxiety and depression), urinary incontinence, and cognitive changes. VMS are among the most common and bothersome menopausal complaints, and one of the main reasons why women may seek medical care for the menopause. Hot flushes are characterized by sudden sensations of heat in the upper body, that last for 2 to 4 minutes and repeat multiple times each day. Up to 80% of menopausal women suffer from VMS, which have a mean duration of 7 to 9 years. About Richter Richter aspires to be a global innovator in some key scientific fields, while dedicated to making medicines more accessible worldwide. Founded in 1901, headquartered in Hungary, with a market capitalization of EUR 4.8bn and sales of EUR 2.3bn in 2025, it operates Central Europe's largest R&D hub. Its research drives breakthroughs in Neuropsychiatry and Women's Healthcare, while Biotechnology and General Medicines strengthen its affordable treatment portfolio. Committed to sustainable growth, Richter invests in R&D, manufacturing excellence, and digitalization to advance medical innovation. Learn more at www.gedeonrichter.com For further information: Investors: Róbert Réthy, CFA +36 20 342 2555 Media: Zsuzsa Beke +36 20 916 4507

临床3期上市批准申请上市临床结果

2026-08-07

·gedeonrichter.com

Richter publishes Q2/H1 2026 results

CER Pharma revenues grew by 8.7%, driven by CNS and BIO and also reflecting improving WHC and GenMed dynamics in Q2. Reported Pharma revenues declined by 0.5% YoY to HUF 455bn in H1 2026, implying around 9ppt currency headwind. CER Clean EBIT (pharma) growth was outstanding at 21%, driven by the outperformance of cariprazine and the benefits of our multi-year efficiency initiatives; reported Clean EBIT (pharma) grew by only 3% to HUF 151.8bn. Net profit was HUF 103.5bn in H1 2026, down by 14% YoY due to large, HUF 27.1bn FX losses burdening the period. Free Cash Flow generation was up by a solid 24% YoY to HUF 137bn. 2026 Clean EBIT guidance (at constant exchange rates, CER) is upgraded to “double-digit growth” on the back of the strong H1 profitability. Budapest, 7 August 2026 - Gedeon Richter Plc. (“Richter”) announced today its Q2/H1 2026 financial results. CER (constant exchange rate) Pharma revenues grew by 8.7% in H1 2026, in line with the high-single-digit growth guidance for the full year and reflected improving dynamics in Q2. FX remains a major drag on reported revenues and represented around 9ppt headwind in H1 (primarily due to the strong HUF). Hence, reported Pharma revenues declined by 0.5% YoY to HUF 455bn in H1 2026. CNS revenues increased by 7% in H1 2026 YoY, as currency movements partly offset the impressive performance of Vraylar® (AbbVie’s net sales increased by 19% YoY to USD 1.98bn reflecting strong demand growth and market share gains in both bipolar disorder and adjunctive MDD) and jumping Reagila® sales (+25% CER, driven by higher supply revenues and high-performing countries in both Richter and partner territories). Women’s Healthcare sales growth (+7% CER in H1) accelerated in Q2 as Endometriosis and Menopause consistently outperform expectations. Lower Eastern European sales and slower dynamics in traditional OC products continue to affect top-line growth. The underlying strength of the leading products (Drovelis®, Ryeqo®, Lenzetto® and Bemfola®) remains intact. BIO revenues jumped in H1 (+30% CER), driven by biosimilar revenues (very strong teriparatide sales and new product launches). GenMed revenues fell by 5% in H1 YoY (CER) although sales dynamics have incrementally been improving. The lack of flu season (weak OTC), a high base and the ongoing rationalization of distributors’ inventory holding affected top-line. Gross profit (pharma) fell by 2.2% YoY to HUF 314bn in H1 2026; gross margin declined to 69% (-1.2ppt), despite improving trends in Q2. CER Clean EBIT (pharma) growth was outstanding at 21% in H1 2026, driven by the outperformance of cariprazine, improving WHC profitability and also supported by lower opex. Reported Clean EBIT (pharma) grew by only 3% to HUF 151.8bn due to the FX headwind. Reported EBIT stood at HUF 143.5bn in H1 2026, 2.2% higher YoY. Net profit (attributable to the owners of the parent) was HUF 103.5bn in H1 2026, declining by 14% YoY, as a result of large, HUF 27.1bn FX losses (mostly unrealized yet) burdening the period as financial expenses. Free cash flow (before M&A) was at another record-high of HUF 137bn in H1 2026, up 24% YoY, driven by lower Net Working Capital funding need vs. a year ago, and higher operating profits, partly offset by FX losses. The multi-year project to optimize and centralize API (active pharmaceutical ingredient) manufacturing in Hungary was completed. The project reduces duplications, improves efficiency, leads to a more compact site structure in Budapest and makes Dorog the API manufacturing site of Richter. Centralizing API manufacturing not only brought in much improved operational efficiency, but also delivered significant environmental benefits. This includes significantly lower energy consumption, materially less overall wastewater and hazardous waste generation, reduced net operational areas and an improved industrial footprint. Gábor Orbán, CEO commented the results: “Top-line growth accelerated in Q2, fully in line with our high-single-digit (CER) growth target for the year, driven by improving dynamics in both Women’s Healthcare and GenMed alongside sustained strength in CNS and BIO revenues. We are upgrading our profitability guidance for 2026 to double-digit Clean EBIT growth (CER), reflecting the outstanding performance of Vraylar® and visible benefits of our multi-year efficiency initiatives. Reported financial results continue to be affected by currency trends. We successfully launched Fylrevy®, an innovative hormone therapy for menopause, in selected pilot markets in Europe; Tuyory®, our tocilizumab biosimilar is now being commercialized; another CNS molecule (RGH-202) is entering Phase II clinical trials; and we further expand our GLP-1 portfolio through global partnerships.” About Gedeon Richter Plc. Richter aspires to be a global innovator in some key scientific fields, while dedicated to making medicines more accessible worldwide. Founded in 1901, headquartered in Hungary, with a market capitalization of EUR 4.8bn and sales of EUR 2.3bn in 2025, it operates Central Europe's largest R&D hub. Its research drives breakthroughs in Neuropsychiatry and Women's Healthcare, while Biotechnology and General Medicines strengthen its affordable treatment portfolio. Committed to sustainable growth, Richter invests in R&D, manufacturing excellence, and digitalization to advance medical innovation. Learn more at www.gedeonrichter.com For further information: Investors: Róbert Réthy, CFA +36 20 342 2555 Media: Zsuzsa Beke +36 20 916 4507

临床2期财报

2026-07-15

·wukong的小筑

生物药PBPK建模：额外清除对人体准确预测的重要性

LITERATURE REVIEW · 文献精读 Pharmaceutics | 2025 Physiologically Based Pharmacokinetic Modeling of Biologic Case Studies in Monkeys and Humans Reveals the Necessity of an Additional Clearance Term Felix Stader1*, Pradeep Sharma2, Weize Huang3, Mary P. Choules4, Marie-Emilie Willemin5, Xinwen Zhang6, Estelle Yau7, Abdallah Derbalah1, Adriana Zyla1, Cong Liu1, Armin Sepp1 1 Certara UK Ltd., Sheffield, UK 2 AstraZeneca, Cambridge, UK 3 Genentech 4 Astellas 5 J&J 6 Amgen 7 Sanofi7跨行业案例(MAB/ADC/BI-TCE)20%CLADD占总清除率比例12.1%猴CMAX平均预测误差2.8%人AUC优化后预测误差0.45人→猴FCRN KD转换系数📌 核心判断本文由Certara牵头、AZ等多家跨国药企联合参与的跨行业合作项目，系统验证了生物药PBPK建模的"learn and confirm"工作流。核心发现：仅需分子量、FcRn结合亲和力和额外系统清除率(CLadd=总清除的20%)三个极简参数即可在食蟹猴中实现准确预测（Cmax误差12.1%，AUC误差−1.9%）。但在人体预测中，不使用CLadd会导致AUC被严重高估（平均+254%），优化后降至+2.8%。这揭示了当前PBPK模型在机械性理解非内皮细胞清除途径方面的根本缺陷，是AZ大分子项目从临床前到临床转化必须正视的方法学瓶颈。1、研究背景与合作框架 PBPK建模在治疗性蛋白（TP）药物开发中的应用日趋重要，但目前缺乏标准化的建模策略。本研究建立了罕见的跨行业协作机制——Certara（Simcyp平台开发商）、AstraZeneca、Genentech、Astellas、Johnson & Johnson、Amgen、Sanofi七家机构各自提供生物药案例，涵盖单克隆抗体（mAb，5例）、抗体偶联药物（ADC，1例）和双特异性T细胞接合器（Bi-TCE，1例）共7个案例研究。研究目标明确：①建立跨生物药类型的PBPK建模工作流；②评估食蟹猴模型是否可用极简参数实现可靠预测；③探究人体预测中额外系统清除率（CLadd）的必要性。这一合作框架本身即反映了行业层面对PBPK标准化策略的共同需求。2、建模策略与关键设计2.1 猴模型：极简参数化方案猴PBPK模型参数化仅需3个输入：①分子量；②与人FcRn的结合亲和力（KD，pH 6.0条件），通过物种转换系数0.45换算为猴FcRn结合参数；③IgG的额外系统清除率，设为总清除率的20%。所有案例均使用非交叉反应物种（猴不识别人靶点），因此不考虑靶标介导的药物处置（TMDD）。模型结构遵循已发表的双孔假说+FcRn回收通路框架：①血管内皮中的内体分选（pH 6.0结合FcRn→回收至血液，未结合→溶酶体降解）；②两孔假说介导的血管-间质分布；③巨胞饮摄取（pinocytosis uptake rate = 0.0298 1/h，基于过氧化物酶标记数据）。组织特异性FcRn丰度取自人源文献，猴数据不足时假设每克组织FcRn含量相同。2.2 人体转化：三场景对比设计人体模拟采用三种平行场景进行对比：①无CLadd（默认模型预测）；②从猴异速标度的CLadd；③优化拟合的CLadd。优化要求剂量足够高以饱和靶点，使TMDD不是限速清除过程。虚拟人群匹配临床研究的受试者数量、性别比例和年龄范围。2.3 评估标准预测误差（PE）用于评价Cmax和AUClast的预测精度，可接受标准定义为PE在−50%至+50%范围内。3、核心结果3.1 猴模型预测精度——极简参数即可胜任预测终点平均PEPE范围评价Cmax+12.1%−20.2% ~ +64.1%轻微高估倾向，1例超出50%边界AUC−1.9%−37.0% ~ +39.4%无系统性偏差，全部在50%边界内尽管仅使用3个极简参数，猴模型的Cmax和AUC预测均达到可接受标准（除1例Cmax外），证明该建模策略在临床前阶段具有高度实用性。另有14项已发表的猴IgG PK研究进一步验证了这一结论。3.2 人体预测：CLadd是成败关键模拟场景CMAX平均PEAUC平均PEAUC PE范围无CLadd（默认）+15.4%+253.9%+53.2% ~ +617.0%异速标度CLadd—改善—优化CLadd—+2.8%−17.0% ~ +44.3% 无CLadd时人体AUC被严重高估（+253.9%），证明现有PBPK模型仅依赖内皮细胞溶酶体降解无法解释实际清除速率。优化CLadd后AUC预测误差降至2.8%，ADC和Bi-TCE的暴露量预测也在50%边界内。异速标度虽改善了预测，但不如优化拟合——3例同时具有猴和人体数据的mAb：默认场景AUC PE为103.6%~347.9%，异速标度降至12.87%~44.5%，优化后进一步降至−4.7%~−9.8%。4、 MIDD方法学视角4.1 CLadd的生物学本质——被忽视的清除途径 CLadd代表的是一组尚未被机械性理解的清除过程：①抗原提呈细胞（APCs）的降解——小鼠研究表明APCs与内皮细胞对IgG降解贡献几乎相等；②非FcRn表达细胞的巨胞饮摄取——心肌细胞、脂肪细胞等摄取TP后在溶酶体中降解；③Fcγ受体介导的摄取——FcγR1可非特异性摄取单体IgG，且其多态性影响利妥昔单抗疗效。这些途径在当前PBPK模型中被简化为经验性CLadd参数。4.2 对AZ大分子项目的直接影响 ① AZ大分子PBPK建模可直接采用本研究的极简参数方案（分子量+人FcRn KD×0.45+CLadd=20%总CL）用于临床前猴PK预测，减少数据需求。② 人体FIH剂量预测必须考虑CLadd，不能仅依赖机制性清除途径。③ 对于ADC和Bi-TCE等新型生物药格式，CLadd策略同样适用（本研究首次在7种不同格式间验证了通用性）。④ 皮下给药生物利用度预测中，APCs在引流淋巴结中饱和FcRn导致的额外降解需特别关注。4.3 从经验参数到机制模型的演进路径研究提出了CLadd机制化的潜在方向：肝细胞通过ASGPR受体介导糖基化蛋白内吞、带正电荷蛋白与细胞膜负电表面的静电相互作用增强摄取、疏水性影响细胞外基质结合等。但将这些因素纳入模型面临参数可识别性挑战——通常只有血浆浓度数据可用，增加过多参数可能导致不可识别。人源化FcRn小鼠（Tg32）模型可作为猴→人转化的中间验证步骤。5、局限性与讨论边界 ① CLadd需要临床数据拟合，目前无法从体外数据直接预测——这是从动物到人体转化的核心瓶颈。② 猴模型的物种转换系数0.45基于有限文献，对不同分子的适用性未逐一验证。③ 案例以mAb为主，ADC仅1例、Bi-TCE仅1例，样本量有限。④ 未涉及肽类或更小分子TP。⑤ 猴模型并非所有案例都有实验数据支撑。⑥ 分子特性（电荷、疏水性、糖基化）对摄取速率的影响尚未量化。关键结论与启示 1. 跨行业7案例验证表明：仅需分子量、FcRn亲和力（人→猴×0.45转换）和CLadd（20%总CL）三个极简参数即可在食蟹猴中实现准确PBPK预测（Cmax PE 12.1%，AUC PE −1.9%） 2. 人体PBPK预测必须引入CLadd项，否则AUC被严重高估（+254%）；优化拟合后AUC PE降至2.8%，异速标度可作为次优替代方案 3. CLadd代表APCs降解、非FcRn细胞巨胞饮和FcγR介导摄取等未被机械性理解的清除途径，是当前PBPK模型从"能用"到"可解释"的关键瓶颈 4. 人源化FcRn小鼠（Tg32）模型可能成为猴→人PBPK转化的重要中间验证环节，有助于独立验证非FcRn依赖的清除机制延伸阅读 Gill KL, Gardner I, Li L, Jamei M A Bottom-up Whole-Body PBPK Model to Mechanistically Predict Tissue Distribution and SC Absorption of Therapeutic Proteins. AAPS J, 2016. DOI→ 推荐理由：本研究所用PBPK模型结构的基础文献 Li L, Gardner I, Dostalek M, Jamei M Simulation of mAb PK in Humans Using a Minimal PBPK Model. AAPS J, 2014. DOI→ 推荐理由：CLadd=20%总CL的来源依据 Richter WF, et al. Hematopoietic Cells as Site of First-Pass Catabolism after SC Dosing and Contributors to Systemic CL of mAb in Mice. mAbs, 2018. DOI→ 推荐理由：APCs对IgG降解贡献的关键实验证据

100 项与雌四醇/屈螺酮相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D12047	雌四醇/屈螺酮	G03AA	-

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痛经	日本	Fuji Pharma Co., Ltd.	2024-09-24
避孕	加拿大	Searchlight Pharma, Inc.	2021-03-05

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盆腔疼痛	临床3期	日本	Fuji Pharma Co., Ltd.	2025-05-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT06396221 (Pubmed \| Sci Rep)	临床4期	-	36	Estetrol drospirenone	壓鬱襯廠鹹積廠糧襯鑰(夢鏇網範蓋醖繭選壓蓋) = 製積構簾網網鹽構觸構積夢餘糧網製衊範獵膚 (觸積構蓋觸築願鏇觸膚 )	非劣	2025-12-12
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NCT04792385 (MIT-Es001-C303, Company_Website) 人工标引	临床3期	避孕	89	ESTELLE	憲簾餘衊選鬱鏇鏇網襯(簾遞簾網夢鬱廠淵壓窪) = no new safety signals were observed. 顧衊憲襯膚餘憲鑰糧餘 (蓋鹹壓遞製齋淵鹹壓鏇 )	积极	2024-04-17
NCT02817841 (CTgov)	临床3期	避孕	2,148	15 mg E4/3 mg DRSP	鑰獵憲餘簾鏇鑰鹹範網 = 願淵鏇範窪願築願淵遞製觸醖襯壓襯衊壓鬱艱 (鏇鬱簾鏇選鹽範顧襯憲, 簾窪艱廠積壓壓觸淵繭 ~ 範鏇網窪蓋蓋築簾簾鹽) 更多	-	2019-11-06
NCT02817828 (CTgov)	临床3期	避孕	1,577	15 mg E4/3 mg DRSP	積繭餘積簾壓鬱顧壓繭 = 鹹襯繭網餘膚網構網構糧遞鬱廠淵鹹築獵範遞 (窪簾艱齋蓋夢膚積窪積, 製鬱憲夢壓選遞遞願繭 ~ 齋構艱鬱鹹夢窪夢構獵) 更多	-	2019-10-04