阿仑膦酸钠/胆骨化醇(Alendronate Sodium/Cholecalciferol) - 药物靶点：VDR_在研适应症：骨质疏松症，绝经期后骨质疏松_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Adrovance、Alendronate Sodium Trihydrate/Colecalciferol、Alendronate Sodium/Colecalciferol

+ [10]

靶点

VDR

作用方式

激动剂、抑制剂

作用机制

VDR激动剂(维生素D受体激动剂)、破骨细胞抑制剂

治疗领域

内分泌与代谢疾病皮肤和肌肉骨骼疾病

在研适应症

骨质疏松症绝经期后骨质疏松

非在研适应症

维生素D缺乏症

原研机构

Merck Sharp & Dohme Corp.

在研机构

Organon NV

Organon & Co.Merck Sharp & Dohme Farmaceutica Ltda.

+ [1]

非在研机构

Merck Sharp & Dohme Corp.

最高研发阶段批准上市

首次获批日期

美国 (2005-04-07),

绝经期后骨质疏松骨质疏松症

最高研发阶段(中国)批准上市

特殊审评-

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结构/序列

分子式C31H63NNaO11P2

InChIKeyZBOIUMYEYAMMKJ-FYLNQELCSA-N

CAS号871265-92-8

关联

14

项与阿仑膦酸钠/胆骨化醇相关的临床试验

CTR20241313

/ Completed临床1期

阿仑膦酸钠维D3片（Ⅱ）在中国健康受试者中空腹给药条件下随机、开放、单剂量、两序列、四周期、完全重复交叉生物等效性试验

按有关药代动力学试验的规定，选择杭州默沙东制药有限公司为生产商的阿仑膦酸钠维D3片（Ⅱ）（商品名：福美加®；规格：每片含阿仑膦酸钠70mg（以阿仑膦酸计）与维生素D3 5600IU（相当于140μg））为参比制剂，对南京九霄药业有限公司持有的受试制剂阿仑膦酸钠维D3片（Ⅱ）（规格：每片含阿仑膦酸钠70mg（以阿仑膦酸计）与维生素D3 5600IU（相当于140μg））进行空腹口服生物等效性试验，比较两种制剂在中国健康志愿者体内的血药浓度经时过程，估算相应的药代动力学参数。同时观察健康受试者口服受试制剂和参比制剂后的安全性。

开始日期2024-05-28

申办/合作机构

南京九霄药业有限公司

EUCTR2019-003101-97-ES

/ Unknown status临床4期IIT

An unicentric, open, randomized and crossover clinical trial to evaluate vitamin D supplementation effect of colecalciferol versus calcidiol in mineral metabolism in hemodialisis patients.

开始日期2020-02-18

申办/合作机构-

NCT02132026

/ Completed临床2期IIT

SALTIRE II: Bisphosphonates and RANKL Inhibition in Aortic Stenosis

Aortic stenosis is a condition whereby one of the heart valves (aortic valve) becomes narrowed, due to calcium deposition, over time. This can lead to chest pain, heart failure and sudden death. It is the commonest valve disease requiring surgery in the developed world and as the population becomes increasingly older, it is predicted that the prevalence of aortic stenosis will double in the next 20 years. Currently the only treatment is replacement of the aortic valve. Whilst this is excellent treatment, not everyone is suitable for it.
The primary objective of our study is to determine whether 2 drugs used in the treatment of osteoporosis (a condition of bone thinning) can halt/retard the progression of aortic stenosis. This is on the basis that studies have suggested that altered regulation of calcium metabolism may be an important mechanism perpetuating the disease. Both drugs work by reducing calcium release into the bloodstream from bones and therefore calcification of the aortic valve.
150 patients will therefore be randomly allocated to either of the trial drugs which are denosumab,the bisphosphonate (alendronic acid), or a placebo.
Positron Emission Tomography (PET) scanning is a technique where biochemically active molecules are injected and are taken up at sites of ongoing calcification activity where they emit radiation and can be detected by the PET scanner. We have previously shown that this technique can demonstrate areas of newly developing calcification on an aortic valve.
We therefore propose that patients receiving bisphosphonates or denosumab will have reduced evidence of active calcification and slower progression of their disease at two years as assessed by Echocardiography (ultrasound) and a change in their calcium score (quantity of calcium on the aortic valve measured using Computed Tomography [CT] ).
The data from this study will then be used to design a larger trial.

开始日期2014-11-12

申办/合作机构

The University of Edinburgh

[+2]

100 项与阿仑膦酸钠/胆骨化醇相关的临床结果

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100 项与阿仑膦酸钠/胆骨化醇相关的转化医学

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100 项与阿仑膦酸钠/胆骨化醇相关的专利（医药）

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100

项与阿仑膦酸钠/胆骨化醇相关的文献（医药）

2025-02-01·World Allergy Organization Journal

Desensitization to colecalciferol in 18 patients with immediate hypersensitivity reactions

Article

作者: Özden, Şeyma ; Atik, Özge ; Can, Ali ; Şaylan, Bengü ; Tepetam, Fatma Merve

Introduction:

Hypersensitivity reactions (HSRs) to colecalciferol (vitamin D) have been rarely reported and the mechanism is unknown. As an alternative treatment was not recommended for vitamin D deficiency, a desensitization protocol with colecalciferol can be performed. We found that there is no standard desensitization protocol for vitamin D. In this study, we aimed to investigate clinical features and skin test results of patients with HSRs to the vitamin D and effectiveness of the 6-step desensitization protocol in which we applied oral drops of colecalciferol.

Method:

This retrospective cross-sectional study included 18 patients with a history of HSRs to oral vitamin D supplements and patients who were planned to receive oral vitamin D replacement. Before desensitization, some of the patients underwent skin tests (skin prick test and intradermal test) with colecalciferol, and the results were recorded. Skin tests were not performed in patients with a history of drug use (antihistamine, systemic steroid, omalizumab, etc.) that affected the results of skin tests. All patients were applied an one bag 6-step desensitization protocol with colecalciferol. Vitamin D3 solution was administered totally 30 drop (4000 IU)/day (1 drop:133.33 IU of 3333 IU/mL) dose of colecalciferol (Devit-3®, DEVA-Türkiye, 15 mL/50,000 IU, 1 mL = 25 drop) at 15-minutes intervals without premedication.

Results:

The patient group consisted of 16 female subjects (89%); the mean age was 46 ± 12 years. When the patients were evaluated in terms of the risk of hypersensitivity reactions according to their clinical history, 5 patients had a history of anaphylaxis with vitamin D preparations (colecalciferol oral drop, n = 3; colecalciferol capsule, n = 2), and 13 patients had a history of HSRs other than anaphylaxis with isolated cutaneous reactions (pruritus, flushing, urticaria and angioedema) (n = 11, colecalciferol oral drop; n = 2, colecalciferol capsule). Skin prick test (SPT) and intradermal test (IDT) were performed on 9 patients. SPTs and IDTs were negative in all patients. Urticaria occur during desensitization in only one patient but vitamin D replacement was performed within the following 48-72 h after HSRs. All other patients tolerated 30 drop (4000 IU) and have continued to take same dose every day for the last 6 weeks with no adverse reactions.

Conclusion:

Desensitization with oral vitamin D preparations has a crucial role for patients who can not receive vitamin D supplements by other ways. Vitamin D drop forms, which are better absorbed than capsule forms which contains the lowest units per/mL without the need to dilute the preparation, not contain any additives with HSRs potential such as gelatin and peanut oil are good option. Our 6-step desensitization protocol with oral drop of colecalciferol is a reliable protocol in patients with a history of vitamin D HSRs.

2024-09-17·Journal of the American Heart Association

Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial

Article

作者: Pawade, Tania A. ; Dweck, Marc R. ; Evans, Emily ; Kwak, Soongu ; Geers, Jolien ; Ralston, Stuart H. ; Newby, David E. ; Tzolos, Evangelos ; Peeters, Frederique E.C.M. ; Bing, Rong ; van Beek, Edwin J. R. ; Forsyth, Laura ; Lucatelli, Christophe ; Fletcher, Alexander J. ; Kwieciński, Jacek ; Slomka, Piotr J ; White, Audrey C. ; Doris, Mhairi K. ; Williams, Michelle C. ; Daghem, Marwa ; Prendergast, Bernard

Background:

Patients with osteoporosis demonstrate increased vascular calcification but the effect of osteoporosis treatments on vascular calcification remains unclear. The present study aimed to examine whether coronary or aortic calcification are influenced by denosumab and alendronic acid treatment.

Methods and Results:

In a double‐blind randomized controlled SALTIRE2 (Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis) trial, patients with aortic stenosis were randomized 2:1:2:1 to denosumab, placebo injection, alendronic acid, or placebo capsule. Participants underwent serial imaging with computed tomography and 18F‐sodium fluoride positron emission tomography for the assessment of vascular calcium burden and calcification activity, respectively. We report the prespecified secondary analyses of 24‐month change in coronary calcium score, and 12‐month changes in thoracic aorta calcium score, coronary and aortic 18F‐sodium fluoride activity. One hundred fifty patients with aortic stenosis (72±8 years; 21% female) were randomized to denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25). There were no differences in change in coronary calcium scores between placebo (16 [−64 to 148] Agatston units) and either denosumab (94 [0–212] Agatston units, P =0.24) or alendronic acid (34 [−62 to 134], P =0.99). There were no differences in change in thoracic aorta calcium scores between placebo (132 [22–512] Agatston units) and either denosumab (118 [11–340], P =0.75) or alendronic acid (116 [26–498] Agatston units, P =0.62). There were no differences in changes in coronary or aortic 18F‐sodium fluoride activity between treatment groups.

Conclusions:

Neither alendronic acid nor denosumab are associated with changes in the activity or progression of coronary or aortic calcification. Osteoporosis treatments do not appear to have major impact on vascular calcification of atherosclerosis.

registration:

https://www.clinicaltrials.gov ; Unique identifier: NCT02132026.

2024-09-01·World journal of otorhinolaryngology - head and neck surgery

Three cases of uncommon medication‐associated osteonecrosis of temporal bone

Article

作者: VanDolah, Hunter ; Kim, H. Jeffrey ; Crossley, Jason R.

Abstract:

Introduction:

Medication‐related osteonecrosis of the temporal bone is rare and has been reported to be associated with the use of anti‐resorptive and biologic agents. Here, we present the first case of tyrosine‐kinase inhibitor‐related external auditory canal (EAC) osteonecrosis as well as two cases related to anti‐resorptive therapies.

Methods:

A retrospective case series.

Results:

Case one: an 84‐year‐old female presented with chronic otitis externa and osteonecrosis of EACs bilaterally. She had a history of osteoporosis treated with denosumab and risedronic acid. She successfully underwent left EAC reconstruction using an inferiorly‐based pedicle periosteal flap while the right ear canal was managed conservatively. Case two: a 69‐year‐old male presented with osteonecrosis of the right EAC. He had a history of osteoporosis treated with alendronic acid and zoledronic acid. His osteonecrosis is conservatively managed with local debridement and antibiotic application. Case three: a 60‐year‐old male presented with osteonecrosis of the right inferior EAC. He had a history of chronic myelogenous leukemia treated with a tyrosine‐kinase inhibitor, imatinib. After failing conservative therapy, he underwent right ear canal reconstruction using a periosteal vascular pedicle flap without complication and experienced complete resolution to his symptoms.

Conclusion:

Anti‐resorptive agents and/or tyrosine kinase inhibitors may lead to dysregulation of bone remodeling and result in rare cases of temporal bone osteonecrosis. When a local debridement and antibiotic therapy fail, definitive surgical excision of necrotic bone with subsequent reconstruction of the EAC may offer patients a possible resolution in symptoms.

1

项与阿仑膦酸钠/胆骨化醇相关的新闻（医药）

2024-08-15

·PMLiVE

NICE recommends Theramex’s Eladynos to treat bone disease after menopause

The National Institute for Health Care and Research has recommended Theramex’s Eladynos (abaloparatide) as an option for treating bone disease after menopause. Available on the NHS in England in three months, the drug is set to benefit more than 14,000 people in the UK who are seeking treatment for osteoporosis after menopause, if there is a very high risk of fracture. Osteoporosis, a bone disease that affects 3.8 million people in the UK, develops when bone mineral density and bone mass decrease, or when the quality or structure of bone changes, leading to a decrease in bone strength that can increase the risk of broken bones or fractures. The disease particularly affects older women after menopause, as oestrogen, the hormone important for maintaining bone density and strength, decreases and bone density reduces, making broken bones more common. Other treatments for the disease include bisphosphonates such as alendronic acid and ibandronic acid, Eli Lilly’s selective oestrogen receptor modulator, Evista (raloxifene), parathyroid hormone treatments including teriparatide, and biological medicines including Amgen’s Prolia (denosumab) and Amgen/UCB’s Evenity (romosozumab). NICE’s decision was based on patients descriptions of how debilitating osteoporosis can be and how it all impacts day-to-day life, impairing mental and physical health. Theramex’s Eladynos is designed to increase bone density by stimulating the cells that produce new bone while also reducing the risk of fracture, providing an alternative for patients who have not responded to or cannot tolerate usual treatment options. Proven to be more clinically and cost-effective, the alternative treatment option comes as a pre-filled pen that is injected into the muscle through the skin. Prior to this, in March, Bayer shared positive long-term results from the late-stage OASIS 3 study, which supported the use of its investigational non-hormonal menopause drug, elinzanetant, to treat moderate-to-severe vasomotor symptoms (VMS), such as hot flashes, which are reported by up to 80% of women during the menopausal transition. In April, a Canadian study published in Neurology revealed that early menopause and a higher risk of cardiovascular disease could be linked to cognitive decline later in life.

临床结果临床3期上市批准

100 项与阿仑膦酸钠/胆骨化醇相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	M05BB03	-

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
骨质疏松症	美国	Organon & Co.	2005-04-07
绝经期后骨质疏松	美国	Organon & Co.	2005-04-07

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10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
维生素D缺乏症	临床3期	-	Merck Sharp & Dohme Corp.	2004-01-01

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临床结果

适应症

分期

评价

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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


WCO_IOF_ESCEO2023	N/A	骨质疏松性骨折	330	Denosumab 60 mg	顧膚願醖願顧餘築淵廠(繭網鏇憲醖觸遞糧糧鏇) = 遞鹽製蓋衊鑰壓範鹽鬱築憲鬱築襯淵選網廠鹹 (壓築襯獵淵範憲鹽壓鹹 )	积极	2023-05-04
				Alendronic acid 70 mg	顧膚願醖願顧餘築淵廠(繭網鏇憲醖觸遞糧糧鏇) = 廠窪鑰膚衊鹹壓憲窪襯築憲鬱築襯淵選網廠鹹 (壓築襯獵淵範憲鹽壓鹹 )
ASN2021	N/A	小管间质性肾炎和葡萄膜炎	-	Alendronic Acid	窪獵範鑰鹽壓繭廠範築(觸膚獵網鏇簾窪鹹鹹醖) = recurrence of her ocular involvement and was diagnosed with anterior uveitis by ophthalmology 網壓廠衊齋鹽艱鏇糧顧 (願齋鬱醖選選糧蓋製鹽 ) 更多	积极	2021-10-27
				Prednisone
WCO_IOF_ESCEO2020	N/A	股骨颈骨折	402	Patients on Alendronic Acid	築獵積壓築夢繭觸鹹鏇(鬱憲積衊範夢醖構製淵) = 餘艱鹽糧艱遞鬱膚衊鏇選壓簾鏇壓製鏇簾築遞 (範壓窪網構膚齋膚顧範 )	-	2020-08-20
				Patients on Drug Holiday	築獵積壓築夢繭觸鹹鏇(鬱憲積衊範夢醖構製淵) = 獵夢遞襯築蓋鹹廠獵醖選壓簾鏇壓製鏇簾築遞 (範壓窪網構膚齋膚顧範 )
[PP.13.08] (ESH2016)	N/A	维生素D缺乏症 25OHD level	109	Cholecalciferol 2000 IE	積壓範築鹽遞築淵艱鬱(廠淵構顧襯鹹願衊糧遞) = 衊窪鑰艱醖築鹹醖繭選鹹鑰網選淵積範遞鬱積 (觸廠鬱繭遞願糧蓋遞齋 )	不佳	2016-09-01
				Placebo	積壓範築鹽遞築淵艱鬱(廠淵構顧襯鹹願衊糧遞) = 醖網廠壓鹽憲獵築構餘鹹鑰網選淵積範遞鬱積 (觸廠鬱繭遞願糧蓋遞齋 )
PP.24.09 (ESH2015)	N/A	-	15	Alendronic acid	蓋積遞夢願壓壓範鹹鏇(鑰艱膚獵鹹艱夢夢餘蓋) = 淵範網夢觸鏇鹹襯選範糧淵襯襯壓遞淵餘齋憲 (築艱淵鏇鏇積選醖願鹹 ) 更多	积极	2015-06-01
				Calcium and vitamin D	蓋積遞夢願壓壓範鹹鏇(鑰艱膚獵鹹艱夢夢餘蓋) = 鹽糧顧鹹鹽膚蓋夢鬱鑰糧淵襯襯壓遞淵餘齋憲 (築艱淵鏇鏇積選醖願鹹 )
NCT00803790 (CTgov)	临床1期	骨质疏松症	318	Vitamin D+Alendronate (Alendronate+Vitamin D Combo)	築繭鹹鹹鹹蓋獵觸築窪(簾顧構膚鏇繭網選醖選) = 選積艱窪鬱壓蓋鏇餘構蓋繭製艱齋繭衊觸齋廠 (艱顧廠構選齋繭夢積壓, 189.2) 更多	-	2011-05-09
				Alendronate (Alendronate)	築繭鹹鹹鹹蓋獵觸築窪(簾顧構膚鏇繭網選醖選) = 淵艱簾糧鹽觸顧繭範蓋蓋繭製艱齋繭衊觸齋廠 (艱顧廠構選齋繭夢積壓, 273.4) 更多
NCT00729651 (0217A-263, CTgov)	临床4期	绝经期后骨质疏松	343	Fosamax (Fosamax Plus D)	範願衊選鹽齋鑰獵齋範 = 廠築夢觸遞憲廠淵獵鹹齋網襯醖廠範壓膚憲觸 (衊醖夢願膚築積鬱願淵, 築鏇壓膚築築餘糧網窪 ~ 壓廠膚衊憲鏇鑰獵網鹽) 更多	-	2010-04-02
				Fosamax (Fosamax)	範願衊選鹽齋鑰獵齋範 = 艱鑰製蓋獵醖壓繭襯襯齋網襯醖廠範壓膚憲觸 (衊醖夢願膚築積鬱願淵, 觸鬱遞積獵襯構衊衊簾 ~ 鹽壓願製壓顧繭鏇壓製) 更多
NCT00806416 (CTgov)	临床1期	骨质疏松症	244	Vitamin D+Alendronate (Alendronate/Vitamin D Combination)	鹽築鹹築鏇夢範膚獵鬱(艱憲鬱顧齋繭選齋積鏇) = 淵壓範構選積鏇夢製憲築衊齋簾夢獵鬱齋鬱鬱 (鏇網製築衊願觸鹹網顧, 329.1) 更多	-	2010-02-12
				Alendronate (Alendronate)	鹽築鹹築鏇夢範膚獵鬱(艱憲鬱顧齋繭選齋積鏇) = 築製鏇遞網製製鹽齋壓築衊齋簾夢獵鬱齋鬱鬱 (鏇網製築衊願觸鹹網顧, 522.2) 更多