The purpose of this study is to find out whether the study drug, metyrapone, is safe and effective in treating participants with Mild Autonomous Cortisol Secretion (MACS).

开始日期2023-12-19

申办/合作机构

Mayo Clinic

NCT05919992 / Recruiting早期临床1期IIT

The Role of Glucocorticoids to Maintain Energy Homeostasis During Starvation

In a randomized, cross-over study, 20 healthy volunteers will receive a block and replace therapy that mimics physiological GC rhythm (metyrapone plus hydrocortisone) or placebo. Participants will undergo two identical fasting periods with each treatment. With the block and replace therapy, fasting-induced GC peak will be suppressed. Metabolic and autonomic parameters will be compared to reveal whether GCs mediate the physiological adaptions to caloric restriction.
Understanding acute effects of GCs upon caloric restriction is critical, since repetitive disruptions of GC secretion may become harmful in chronic conditions.

开始日期2023-05-15

申办/合作机构-

NCT05255900 / RecruitingN/AIIT

Metabolic, Pressor and Neuropsychological Effects of Metyrapone Treatment in Patients With Hypercortisolism

The aims of the present study are to evaluate in patients with mild hypercortisolism the effect of metyrapone treatment on glycometabolic control, blood pressure, thrombotic risk parameters, lipid profile, bone turnover markers, mental health and cortisol circadian rhythm.

开始日期2022-04-28

申办/合作机构

Istituto Auxologico Italiano

[+1]

100 项与美替拉酮相关的临床结果

登录后查看更多信息

100 项与美替拉酮相关的转化医学

登录后查看更多信息

100 项与美替拉酮相关的专利（医药）

登录后查看更多信息

3,546

项与美替拉酮相关的文献（医药）

2024-01-08·JCEM case reports

Prolonged Hypokalemia Following Metyrapone Treatment for Primary Bilateral Macronodular Adrenal Cortical Disease

作者: Kakutani-Hatayama, Miki ; Kidawara, Yonekazu ; Koyama, Hidenori ; Fukuoka, Hidenori

Abstract:

Surgical treatment is generally the standard therapeutic regimen used for primary bilateral macronodular adrenal cortical disease (PBMACD). However, in cases for which surgery is difficult or in which there is mild cortisol hypersecretion, metyrapone treatment can be selected. Although hypokalemia has been occasionally noted following metyrapone administration for Cushing syndrome associated with an adrenal adenoma, all such cases have been reported to be transient. Hypokalemia induced by metyrapone treatment is thought to occur due to excessive suppression of cortisol secretion, resulting in overproduction of adrenocorticotropic hormone from the pituitary gland, ultimately leading to excessive production of 11-deoxycorticosterone (DOC) in the adrenal cortex. A 52-year-old man diagnosed with PBMACD and started on metyrapone treatment subsequently presented with persistent hypokalemia. Interestingly, following initiation of metyrapone, blood test findings indicated marginal changes in serum cortisol, adrenocorticotropic hormone, and dehydroepiandrosterone sulfate levels, even when DOC levels were already markedly elevated. In addition to the effects of metyrapone, the present findings suggest a unique DOC synthesis regulatory mechanism involved in the pathogenesis of PBMACD.

2024-02-01·Comparative biochemistry and physiology. Part A, Molecular & integrative physiology

Cortisol enhances aerobic metabolism and locomotor performance during the transition to land in an amphibious fish

Article

作者: Wright, Patricia A ; Rossi, Giulia S ; Bernier, Nicholas J ; Young, Sarah J

Amphibious fishes on land encounter higher oxygen (O₂) availability and novel energetic demands, which impacts metabolism. Previous work on the amphibious mangrove killifish (Kryptolebias marmoratus) has shown that cortisol becomes elevated in response to air exposure, suggesting a possible role in regulating metabolism as fish move into terrestrial environments. We tested the hypothesis that cortisol is the mechanism by which oxidative processes are upregulated during the transition to land in amphibious fishes. We used two groups of fish, treated fish (+metyrapone, a cortisol synthesis inhibitor) and control (-metyrapone), to determine the impact of cortisol during air exposure (0 and 1 h, 7 days) on O₂ consumption, terrestrial locomotion, the phenotype of red skeletal muscle, and muscle lipid concentration. Metyrapone-treated fish had an attenuated elevation in O₂ consumption rate during the water to air transition and an immediate reduction in terrestrial exercise performance relative to control fish. In contrast, we found no short- (0 h) or long-term (7 days) differences between treatments in the oxidative phenotype of red muscles, nor in muscle lipid concentrations. Our results suggest that cortisol stimulates the necessary increase in aerobic metabolism needed to fuel the physiological changes that amphibious fishes undergo during the acclimation to air, although further studies are required to determine specific mechanisms of cortisol regulation.

2024-02-01·Data in brief

Transcriptomic data of human adrenocortical NCI-H295R cells treated with cortisol biosynthesis inhibitors

Article

作者: Jung, Jong-Wha ; Chung, Sooyoung ; Son, Gi Hoon ; Kim, Soo Hyun ; Kim, Hyun Jung

Adrenal corticosteroid biosynthesis dysregulation can give rise to various pathological conditions, such as Cushing's syndrome, a disorder characterized by the sustained and excessive production of cortisol. Despite the development of several classes of steroidogenesis inhibitors to treat human diseases associated with cortisol overproduction, their use is limited by insufficient efficacy, adverse effects, and/or tolerability. Recently, we identified a series of benzimidazolylurea derivatives, including the representative compound CJ28, as novel cortisol biosynthesis inhibitors [1]. They significantly inhibited both basal and stimulated production of cortisol in NCI-H295R cells, a human adrenocarcinoma cell line. The inhibitory effects were attributed to both attenuated steroidogenesis and de novo cholesterol biosynthesis. Here, we provide transcriptomic (RNA-seq) data from adrenal cell cultures in response to treatment with either CJ28 or metyrapone (MET), an inhibitor of 11β-hydroxylase). Total RNA was extracted from the cells treated with vehicle (0.1% DMSO), CJ28 (30 µM), or MET (30 µM) for 24 h. Primary sequence data were acquired using paired-end sequencing on an Illumina NovaSeq 6000 platform. The raw RNA-seq data have been deposited in the Gene Expression Omnibus (GEO) database (GSE236435). This dataset is a useful resource for providing valuable information on the gene expression networks underlying adrenocortical steroidogenesis.

项与美替拉酮相关的新闻（医药）

2024-05-30

·蒲公英Ouryao

又有35个品规儿童药鼓励研发申报

转自：国家卫健委编辑：水晶5月30日，国家卫健委药物政策与基本药物制度司公示第五批鼓励研发申报儿童药品建议清单。公示清单共35个品规，这些品规是国内未注册上市且临床急需的儿童用药。35个第五批公示品规：阿尼芬净（注射剂）、柯拉特龙（乳膏剂）、头孢罗膦（注射剂）、艾伐卡托（颗粒剂）、阿托伐他汀混悬剂、达比加群酯（微丸）、索利那新（混悬剂）、托吡酯（口服溶液剂）、托法替布（口服溶液剂）、西替利嗪（注射剂）、伊伐雷定（口服溶液剂）、氨曲南（吸入溶液剂) 、甲苯磺酸托氟沙星（颗粒剂、片剂）、美替拉酮（胶囊剂）、谷卡匹酶（注射剂）、舒噻美（口服混悬液）、匹莫齐特（片剂）、培维索孟（注射液）、阿昔单抗（注射剂）、瑞斯利珠单抗（注射剂）、卡拉西珠单抗（注射剂）、艾哌依卡基（注射剂）、瑞利珠单抗（注射剂）。第四批24个品种：涉及30个品规、9种剂型，覆盖神经系统用药、消化道和新陈代谢用药、抗肿瘤药及免疫调节剂等治疗领域。<<详见24个品种！四部门联合印发（第四批）鼓励研发申报儿童药品清单>>前三批105种：2016年以来，国家卫生健康委会同有关部门，先后制定并发布了三批含105种药品的《鼓励研发申报儿童药品清单》。为进一步落实原国家卫生计生委等6部门《关于保障儿童用药的若干意见》要求，丰富儿童适用药品的品种、剂型和规格，满足儿科临床用药需求，2024年，国家卫生健康委、工业和信息化部和国家药监局继续紧密围绕我国儿童疾病谱以及相关企业研发生产能力，组织临床、药学、研发、注册等有关专家结合中国大陆境内尚未注册上市且临床急需的儿童用药现状，基于循证原则筛选论证，提出了《第五批鼓励研发申报儿童药品建议清单》。现予以公示，公示5个工作日。如有异议，请通过以下电话予以反映。电话：（010）68791740 附件：第五批鼓励研发申报儿童药品建议清单药物政策与基本药物制度司 2024年5月30日

上市批准

2024-04-26

·Firstwordpharma

Perrigo to divest rare diseases unit to Spain's Esteve for €275 million

Perrigo is offloading its HRA Pharma Rare Diseases business to Barcelona-based pharmaceutical company Esteve Healthcare for a total of up to €275 million ($294 million) and plans to use the proceeds to help pay down its debt.The transaction, which includes €190 million in cash upfront plus up to €85 million in potential earnouts if certain sales targets are reached, is expected to close in the third quarter.The unit's three-product portfolio includes the Cushing's syndrome treatments Metopirone (metyrapone) and ketoconazole, as well as Lysodren (mitotane), which is prescribed to treat adrenal cortical carcinoma. Staffan Schüberg, chief executive at Esteve, said the deal is "another step towards the company's vision of being an international and specialist pharma company."Meanwhile, Perrigo CEO Patrick Lockwood-Taylor said the divestment "further supports our position as a leading fast-moving consumer goods company," adding that the upfront cash proceeds would allow the company "to reduce net leverage to below 4.0x by the end of 2024."

并购上市批准

2023-05-09

·Pharmaceutical Technology

FibroGen and Fortis sign exclusive licence deal for mCRPC drug candidate

FOR46 is being developed as a potential treatment for metastatic castration-resistant prostate cancer. Credit: Nephron/commons.wikimedia.org FibroGen has signed an exclusive licence agreement with Fortis Therapeutics for the FOR46 antibody-drug conjugate (ADC) that targets a new epitope on CD46, a protein-coding gene. FOR46 is currently being investigated in a Phase I trial as a potential treatment for metastatic castration-resistant prostate cancer (mCRPC). Recommended Reports Reports LOA and PTSR Model - (Metyrapone + Oxazepam) in Substance (Drug) Abuse GlobalData Reports LOA and PTSR Model - Esmethadone Hydrochloride in Substance (Drug) Abuse GlobalData View all The trial is also studying the capability of FOR46 for use in other CD46-expressing cancers. The new deal, which does not include any initial consideration, will see FibroGen conducting and financing new research, development and production of FOR46 and PET46. Throughout the deal’s four-year evaluation period, FibroGen has an option to buy Fortis Therapeutics for $80m. Fortis can also receive up to $200m in total on the basis of multiple regulatory approvals. Under the clinical development strategy, FibroGen will continue the work of Fortis Therapeutics to develop a PET-based biomarker using a radiolabeled version of the targeting antibody (PET46) for selecting patients. FibroGen CEO Enrique Conterno stated: “The agreement with Fortis Therapeutics bolsters FibroGen’s clinical pipeline in a capital-efficient manner, providing a product candidate with the potential to address a significant unmet medical need in oncology. “FOR46 is a natural fit with our research and development capabilities and expertise. “The flexibility of the agreement gives us the opportunity to clinically develop FOR46, and ultimately acquire it as a Phase III-ready asset, potentially delivering a therapy that may transform the treatment of patients with mCRPC and other CD46-expressing cancers.” In early May 2023, FibroGen announced that it would receive a $150m non-dilutive term loan facility from funds managed by Morgan Stanley Tactical Value (MSTV) to accelerate the commercialisation of pamrevlumab.

临床1期引进/卖出抗体药物偶联物并购

100 项与美替拉酮相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D00410	美替拉酮	V04CD01	DB01011

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
肾上腺皮质功能不全	-	Novartis AG	2014-05-30
库欣综合征	澳大利亚	CHIESI Farmaceutici SpA	1991-08-02
垂体ACTH分泌过多	美国	HRA Pharma Rare Diseases SAS	1961-12-04

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
内源性库欣综合征	临床3期	比利时	HRA Pharma Development SARL	2015-04-01
内源性库欣综合征	临床3期	德国	HRA Pharma Development SARL	2015-04-01
内源性库欣综合征	临床3期	匈牙利	HRA Pharma Development SARL	2015-04-01
内源性库欣综合征	临床3期	意大利	HRA Pharma Development SARL	2015-04-01
内源性库欣综合征	临床3期	波兰	HRA Pharma Development SARL	2015-04-01
内源性库欣综合征	临床3期	罗马尼亚	HRA Pharma Development SARL	2015-04-01
内源性库欣综合征	临床3期	西班牙	HRA Pharma Development SARL	2015-04-01
内源性库欣综合征	临床3期	土耳其	HRA Pharma Development SARL	2015-04-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ESPE2016	N/A	库欣综合征	-	Metyrapone	醖憲獵憲膚齋憲廠願衊(艱鹹餘餘獵遞衊廠鹹艱) = 廠選鹹壓範築艱醖鑰製壓醖齋積窪鬱艱艱遞蓋 (築糧壓齋簾觸醖積壓構 )	-	2016-09-10
Pubmed	N/A	库欣综合征	195	Metyrapone	廠積襯淵簾範壓網鏇繭(製鏇餘顧膚艱艱廠積襯) = 顧顧顧齋憲壓製鏇製蓋夢繭選醖簾獵鑰遞齋廠 (襯衊範齋積餘淵壓選構 ) 更多	积极	2015-11-01