更新于：2024-12-14

Prochlorperazine

丙氯拉嗪

更新于：2024-12-14

概要

概要

基本信息

药物类型

小分子化药

别名

2-Chloro-10-(3-(1-methyl-4-piperazinyl)propyl)-phenothiazine、2-Chloro-10-(3-(4-methyl-1-piperazinyl)propyl)phenothiazine、3-Chloro-10-(3-(1-methyl-4-piperazinyl)propyl)phenothiazine

+ [11]

靶点

D2 receptor

作用机制

D2 receptor拮抗剂(多巴胺D2受体拮抗剂)

治疗领域

其他疾病

在研适应症-

非在研适应症

精神分裂症

原研机构

GSK Plc

在研机构-

非在研机构

GlaxoSmithKline, Inc.

最高研发阶段撤市

首次获批日期

美国 (1959-01-26),

精神分裂症

最高研发阶段(中国)-

特殊审评-

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结构

分子式C20H24ClN3S

InChIKeyWIKYUJGCLQQFNW-UHFFFAOYSA-N

CAS号58-38-8

关联

项与丙氯拉嗪相关的临床试验

CTRI/2024/10/075430 / Recruiting临床4期

A Multi-Centric, Prospective, Single Arm, Open label Post Marketing Observational Study To Assess The Effectiveness And Safety Of Oral Prochlorperazine In Acute Phase In Patients Diagnosed With Benign Paroxysmal Positional Vertigo (BPPV). - NIL

开始日期2024-11-10

申办/合作机构-

CTRI/2024/08/072429 / Not yet recruiting临床3期

An open-label phase III randomized controlled trial comparing metoclopramide, thalidomide, prochlorperazine, and lorazepam for treating breakthrough chemotherapy-induced nausea and vomiting in patients receiving olanzapine as part of antiemetic prophylaxis for highly emetogenic chemotherapy. - Nil

开始日期2024-09-01

申办/合作机构-

ACTRN12624000917538 / Not yet recruiting临床2期IIT

Efficacy and safety of cetuximab and prochlorperazine combined for solid organ transplant patients with advanced Cutaneous Squamous Cell Carcinoma: CetPro study

开始日期2024-08-01

申办/合作机构

The University of Queensland

100 项与丙氯拉嗪相关的临床结果

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100 项与丙氯拉嗪相关的转化医学

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100 项与丙氯拉嗪相关的专利（医药）

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1,078

项与丙氯拉嗪相关的文献（医药）

2025-01-01·AMERICAN JOURNAL OF EMERGENCY MEDICINE

A prospective single-blinded randomized field-based trial to evaluate the prophylactic treatment of oral prochlorperazine for acute mountain sickness

Letter

作者: White, Joshua ; Sample, Laura ; Xu, K. Tom ; Miller, Michael ; Vanderkooi, Kayla ; Richman, Peter ; Xu, K Tom

2025-01-01·JOURNAL OF PEDIATRICS

An Eye-Opening Episode: Oculogyric Crisis Precipitated by Prochlorperazine

Article

作者: Silverman, Andrew ; Cheronis, Chrisoula

2024-08-01·JAMA Internal Medicine

Severe Acute Liver Injury After Hepatotoxic Medication Initiation in Real-World Data

Article

作者: Njei, Basile ; Mezochow, Alyssa K ; Bhattacharya, Debika ; Bräu, Norbert ; Lo Re, Vincent ; Tate, Janet P ; Torgersen, Jessie ; Carbonari, Dean M. ; Rentsch, Christopher T ; Newcomb, Craig W ; Lim, Joseph K ; Justice, Amy C ; Roy, Jason A ; Mezzacappa, Catherine ; Carbonari, Dena M ; Park, Lesley S ; Taddei, Tamar H ; Hennessy, Sean

Importance:

Current approaches to classify the hepatotoxic potential of medications are based on cumulative case reports of acute liver injury (ALI), which do not consider the size of the exposed population. There is little evidence from real-world data (data relating to patient health status and/or the delivery of health care routinely collected from sources outside of a research setting) on incidence rates of severe ALI after initiation of medications, accounting for duration of exposure.

Objective:

To identify the most potentially hepatotoxic medications based on real-world incidence rates of severe ALI and to examine how these rates compare with categorization based on case reports.

Design, Setting, and Participants:

This series of cohort studies obtained data from the US Department of Veterans Affairs on persons without preexisting liver or biliary disease who initiated a suspected hepatotoxic medication in the outpatient setting between October 1, 2000, and September 30, 2021. Data were analyzed from June 2020 to November 2023.

Exposures:

Outpatient initiation of any one of 194 medications with 4 or more published reports of hepatotoxicity.

Main Outcomes and Measures:

Hospitalization for severe ALI, defined by either inpatient: (1) alanine aminotransferase level greater than 120 U/L plus total bilirubin level greater than 2.0 mg/dL or (2) international normalized ratio of 1.5 or higher plus total bilirubin level greater than 2.0 mg/dL recorded within the first 2 days of admission. Acute or chronic liver or biliary disease diagnosis recorded during follow-up or as a discharge diagnosis of a hospitalization for severe ALI resulted in censoring. This study calculated age- and sex-adjusted incidence rates of severe ALI and compared observed rates with hepatotoxicity categories based on cumulative published case reports.

Results:

The study included 7 899 888 patients across 194 medication cohorts (mean [SD] age, 64.4 [16.4] years, 7 305 558 males [92.5%], 4 354 136 individuals [55.1%] had polypharmacy). Incidence rates of severe ALI ranged from 0 events per 10 000 person-years (candesartan, minocycline) to 86.4 events per 10 000 person-years (stavudine). Seven medications (stavudine, erlotinib, lenalidomide or thalidomide, chlorpromazine, metronidazole, prochlorperazine, and isoniazid) exhibited rates of 10.0 or more events per 10 000 person-years, and 10 (moxifloxacin, azathioprine, levofloxacin, clarithromycin, ketoconazole, fluconazole, captopril, amoxicillin-clavulanate, sulfamethoxazole-trimethoprim, and ciprofloxacin) had rates between 5.0 and 9.9 events per 10 000 person-years. Of these 17 medications with the highest observed rates of severe ALI, 11 (64%) were not included in the highest hepatotoxicity category when based on case reports.

Conclusions and Relevance:

In this study, incidence rates of severe ALI using real-world data identified the most potentially hepatotoxic medications and can serve as a tool to investigate hepatotoxicity safety signals obtained from case reports. Case report counts did not accurately reflect the observed rates of severe ALI after medication initiation.

项与丙氯拉嗪相关的新闻（医药）

2024-11-05

·ioncology

SABCS 2024丨乳腺癌领域年终盛典将至，重磅研究汇总！

点击蓝字，关注我们编者按：第47届圣安东尼奥乳腺癌研讨会（SABCS）将于当地时间2024年12月10日至13日在美国得克萨斯州圣安东尼奥举行。日前，官网已公布摘要题目，肿瘤瞭望特将Late-Breaking Oral Presentations、General Session、Rapid Fire、Poster Spotlight Sessions等环节口头报告内容进行整理，敬请关注！ Late-Breaking Oral Presentations 时间：12月10日6:00 – 7:00 pm 地点：Stars at Night 1-2 主持人：Rita Nanda, University of Chicago Medicine, Chicago, Illinois LB1-01: Long-term effects of the omission of immediate surgery in operable breast cancer, or reduction of surgical extent: patient-level meta-analysis of the four randomised trials among 2,514 women. 可手术乳腺癌中省略即刻手术或缩小手术范围的长期影响：基于2514名女性的四项随机试验患者层面的荟萃分析讲者：Robert Hills, University of Oxford, Oxford, United Kingdom LB1-02: MARGOT/TBCRC052: A randomized phase II trial comparing neoadjuvant paclitaxel/margetuximab/pertuzumab (TMP) vs paclitaxel/trastuzumab/pertuzumab (THP) in patients (pts) with stage II-III HER2+ breast cancer. MARGOT/TBCRC052：一项随机II期临床试验，比较II-III期HER2阳性乳腺癌患者中新辅助治疗帕妥珠单抗/马吉妥昔单抗/紫杉醇（TMP）vs帕妥珠单抗/曲妥珠单抗/紫杉醇（THP）的疗效讲者：Adrienne Waks, Dana-Farber Cancer Institute, Boston, Massachusetts LB1-03: Primary results of the randomised Phase III trial comparing first-line ET plus palbociclib vs standard mono-chemotherapy in women with high risk HER2-/HR+ metastatic breast cancer and indication for chemotherapy - PADMA study. PADMA研究：比较高危HR+/HER2-转移性乳腺癌女性患者一线ET联合哌柏西利vs标准单药化疗的随机III期试验的主要结果讲者：Sibylle Loibl, German Cooperative Group, Neu-Isenburg, Germany LB1-04: Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) by pace of disease progression on prior endocrine-based therapy: additional analysis from DESTINY-Breast06. 基于既往内分泌治疗的疾病进展速度，比较德曲妥珠单抗（T-DXd） vs医生选择的化疗（TPC）的疗效与安全性：来自DESTINY-Breast06的额外分析讲者：Aditya Bardia, UCLA David Geffen School of Medicine, Los Angeles, California LB1-05: ROSC (Neo)adjuvant nab-PAC weekly vs sb-PAC q2w, followed by EC q2w, in genomically or clinically high-risk HR+/HER- early breast cancer according to ET-response: final survival results from the WSG ADAPT-HR+/HER2- chemotherapy-trial. 在遗传或临床高危HR+/HER2-早期乳腺癌中，根据ET反应（新）辅助nab-PAC周疗 vs 每2周1次sb-PAC，随后每2周1次EC：WSG ADAPT-HR+/HER2-化疗试验最终生存结果讲者：Sherko Kuemmel, German Medical Institute, Limassol, Germany LB1-06: Primary results of SOLTI VALENTINE: neoadjuvant randomized phase II trial of HER3-DXd alone or in combination with letrozole for high-risk hormone receptor positive (HR+)/HER2-negative (neg) early breast cancer (EBC). SOLTI VALENTINE研究的主要结果：针对高风险HR+/HER2-早期乳腺癌（EBC），比较单独使用HER3-DXd或联合使用来曲唑新辅助治疗的随机II期试验讲者：Mafalda Oliveira, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain LB1-07: Exploratory Biomarker Analysis of the Phase 3 KEYNOTE-522 Study of Neoadjuvant Pembrolizumab or Placebo Plus Chemotherapy Followed by Adjuvant Pembrolizumab or Placebo for Early-Stage TNBC. 3期KEYNOTE-522研究生物标志物探索性分析：对早期TNBC患者用帕博利珠单抗或安慰剂联合化疗进行新辅助治疗，随后用帕博利珠单抗或安慰剂进行辅助治疗讲者：Joyce O’Shaughnessy, Baylor-Sammons Cancer Center, Dallas, Texas General Session 1 时间：12月11日9:15 – 11:30 am 地点：Hall 1 GS1-01: Imlunestrant, an Oral Selective Estrogen Receptor Degrader (SERD), as Monotherapy and Combined with Abemaciclib, for Patients w/ ER+, HER2- Advanced Breast Cancer (ABC), Pretreated w/ Endocrine Therapy (ET): Results of the Phase 3 EMBER-3 trial. 口服选择性雌激素受体降解剂（SERD）Imlunestrant单药治疗及联合阿贝西利治疗既往接受内分泌治疗（ET）的雌激素受体阳性（ER+）、人表皮生长因子受体2阴性（HER2-）晚期乳腺癌（ABC）患者的疗效：III期EMBER-3研究结果讲者：Komal Jhaveri, Memorial Sloan Kettering Cancer Center, New York, New York GS1-03: Pyrotinib or placebo in combination with trastuzumab and docetaxel for untreated HER2-positive metastatic breast cancer (mBC): prespecified final analysis of progression-free survival (PFS) of the phase 3 PHILA trial. 吡咯替尼或安慰剂联合曲妥珠单抗和多西他赛用于未接受过治疗的HER2阳性转移性乳腺癌（mBC）：III期PHILA试验预设的无进展生存期（PFS）最终分析讲者：徐兵河（中国医学科学院肿瘤医院） GS1-04: HER2-Directed Antibody-Drug Conjugate SHR-A1811 in the Neoadjuvant Treatment of HER2-positive Early Breast Cancer: a Prospective, Randomized, Open-label, Phase 2 Trial. 靶向HER2的抗体-药物偶联物SHR-A1811用于HER2阳性早期乳腺癌的新辅助治疗：一项前瞻性、随机、开放标签的2期试验讲者：李俊杰（复旦大学附属肿瘤医院） GS1-06: PRO B – a superiority randomized controlled trial evaluating the effects of symptom monitoring in metastatic breast cancer patients. PRO B ——一项评估转移性乳腺癌患者症状监测效果的优效性随机对照试验讲者：Maria Margarete Karsten, Charité-Universitätsmedizin, Berlin GS1-08: Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: results from an international cohort study. 年轻乳腺癌患者中BRCA携带者接受降低风险性手术与生存期之间的关联：一项国际队列研究结果讲者：Matteo Lambertini, University of Genova, Genova, Italy GS1-09: OlympiA- Phase 3, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients w/ germline BRCA1/BRCA2 pathogenic variants & high risk HER2-negative primary breast cancer; longer term follow. OlympiA长期随访——一项针对携带胚系BRCA1/BRCA2致病性变异且高危HER2阴性原发性乳腺癌患者，在（新）辅助化疗后使用辅助奥拉帕利（olaparib）的III期、多中心、随机、安慰剂对照试验讲者：Judy Garber, Dana-Farber Cancer Institute, Boston, Massachusetts Rapid Fire 1 时间：12月11日12:00 – 12:50 pm 地点：Stars at Night 1-2 主持人：Moderator: Shom Goel, University of Melbourne Peter MacCallum Cancer Centre RF1-01: Effect of a weight loss intervention (WLI) on metabolic and inflammatory biomarkers in women with obesity and breast cancer: Results from the Breast Cancer Weight Loss (BWEL) Trial (Alliance). 减重干预（WLI）对肥胖合并乳腺癌女性的代谢和炎症生物标志物的影响：乳腺癌减重（BWEL）试验（Alliance）的结果讲者：Jennifer Ligibel, Dana-Farber Cancer Institute, Boston, Massachusetts RF1-02: Palbociclib plus letrozole versus weekly paclitaxel, both in combination w/ trastuzumab plus pertuzumab, as neoadjuvant treatment for patients w/ HR+/HER2+ early breast cancer: primary results from the randomized phase II TOUCH trial (IBCSG 55-17). 哌柏西利联合来曲唑对比周疗紫杉醇，两者均与曲妥珠单抗和帕妥珠单抗联用，作为HR+/HER2+早期乳腺癌患者的新辅助治疗：来自II期TOUCH随机试验（IBCSG 55-17）的主要结果讲者：Luca Malorni, USL Toscana Centro, Hospital of Prato, Prato, Italy RF1-03: Three-year event-free survival (EFS) of the multicenter phase II TRAIN-3 study evaluating image-guided optimization of neoadjuvant chemotherapy duration in stage II and III HER2-positive breast cancer (BOOG 2018-01). 多中心II期TRAIN-3研究评估了II期和III期HER2阳性乳腺癌（BOOG 2018-01）中基于影像引导的新辅助化疗持续时间优化的三年无事件生存率（EFS）讲者：Fleur Louis, Antoni van Leeuwenhoekziekenhuis, Amsterdam, Netherlands RF1-04: Long-Term Follow-up and updated analysis from S0221, Comparing Alternative Dose-Schedules of Adjuvant Anthracycline/Taxane Therapy in High-Risk Early Breast Cancer. S0221研究长期随访与更新分析：比较蒽环类/紫杉类辅助治疗高危早期乳腺癌的替代剂量方案讲者：Azka Ali, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois RF1-05: DNA methylation patterns are similar in benign tissue from ipsilateral and contralateral breast while different from matched breast cancer, and healthy controls. 同侧与对侧乳房的良性组织中的DNA甲基化模式相似，但与配对的乳腺癌组织和健康对照组存在差异讲者：Saya Dennis, Northwestern University Feinberg School of Medicine, Chicago, Illinois RF1-06: Association of polygenic-based breast cancer risk prediction with patient management. 基于多基因的乳腺癌风险预测与患者管理的相关性讲者：Katie Johansen Taber, Myriad Genetics, San Francisco, California RF1-07: Multifactor analysis for pathologic complete response (pCR) in a chemotherapy-free regimen of durvalumab, trastuzumab, and pertuzumab (DTP Trial) in HER2-enriched early breast cancer. 在HER2过表达的早期乳腺癌中，不含化疗的度伐利尤单抗、曲妥珠单抗和帕妥珠单抗方案（DTP研究）的病理完全缓解（pCR）的多因素分析讲者：Bojana Stefanovska, UT Health Science Center, San Antonio, Texas General Session 2 时间：12月12日9:00–11:45 am 地点：Hall 1 GS2-01: Exclusive endocrine therapy or radiation therapy in women aged 70+ years with luminal-like early breast cancer (EUROPA): preplanned interim analysis of a randomized phase 3 trial. 随机3期EUROPA研究预先计划的期中分析：70岁以上luminal型早期乳腺癌女性患者单纯内分泌治疗或放疗的疗效讲者：Icro Meattini, University of Florence, Florence, Italy GS2-02: Impact of Tamoxifen Only after Breast Conservation Surgery for "Good Risk" Duct Carcinoma in Situ: Results from the NRG Oncology/RTOG 9804 and ECOG-ACRIN E5194 Trial “低风险”原位导管癌保乳术后仅采用他莫昔芬治疗的影响：NRG Oncology/RTOG 9804和ECOG-ACRIN E5194试验的结果讲者：Jean Wright, University of North Carolina School of Medicine, Chapel Hill, North Carolina GS2-03: Does postmastectomy radiotherapy in 'intermediate-risk' breast cancer impact overall survival? 10-year results of the BIG 2-04 MRC SUPREMO randomised trial: on behalf of the SUPREMO trial investigators. “中危”乳腺癌患者术后放疗是否影响总生存期？BIG 2-04 MRC SUPREMO随机试验10年结果：代表SUPREMO试验研究者讲者：Ian Kunkler, Edinburgh Cancer Centre, University of Edinburgh, Edinburgh, Scotland GS2-05: Early Oncologic Outcomes Following Active Monitoring or Surgery (+/- Radiation) for Low Risk DCIS: the Comparing an Operation to Monitoring, with or without Endocrine Therapy (COMET) Study (AFT-25). 低危导管原位癌（DCIS）患者主动监测或手术（±放疗）后的早期肿瘤学结局：比较手术与监测伴或不伴内分泌治疗（COMET）研究（AFT-25）讲者：Eun-Sil Hwang, Duke University School of Medicine, Durham, North Carolina GS2-06: Patient Reported Outcomes Following Active Monitoring or Surgery (+/- Radiation) for Low Risk DCIS in the Comparing an Operation to Monitoring, with or without Endocrine Therapy (COMET) Study (AFT-25). 低危导管原位癌（DCIS）患者主动监测或手术（±放疗）后的患者报告结局：比较手术与监测伴或不伴内分泌治疗（COMET）研究（AFT-25）讲者：Ann Partridge, Dana-Farber Cancer Institute, Boston, Massachusetts GS2-07: No axillary surgery versus axillary sentinel lymph node biopsy in patients with early invasive breast cancer and breast-conserving surgery: Final primary results of the Intergroup-Sentinel-Mamma (INSEMA) trial. 早期浸润性乳腺癌患者不接受腋窝手术vs接受保乳手术的腋窝前哨淋巴结活检比较：INSEMA（intergroup sentinel - mamma）试验的最终主要结果讲者：Toralf Reimer, Universitätsmedizin Rostock, Rostock, Germany GS2-09: Overweight, obesity and prognosis in 206,904 women in the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) database. 早期乳腺癌试验协作组（Early Breast Cancer trials’Collaborative Group，EBCTCG）数据库中206904名女性的超重、肥胖和预后情况讲者：Hongchao Pan, University of Oxford, Oxford, United Kingdom GS2-10: A long-term image-derived AI risk model for primary prevention of breast cancer. 用于乳腺癌一级预防的基于长期图像衍生的AI风险模型讲者：Mikael Eriksson, Karolinska Institutet, Solna, Sweden GS2-11: APOBEC3 mutagenesis induces resistance-promoting genomic alterations in breast cancer. APOBEC3突变诱导乳腺癌中促进耐药的基因组改变讲者：Avantika Gupta, Memorial Sloan Kettering Cancer Center, New York, New York Rapid Fire 2 时间：12月12日12:00 – 12:50 pm 地点：Hall 1 主持人：Carlos Arteaga, UT Southwestern, Dallas, Texas RF2-01: Factors Influencing Additional Nodal Disease and Pathologic Nodal Upstaging with Axillary Dissection in Patients with Residual Node-Positive Breast Cancer After Neoadjuvant Chemotherapy Enrolled on Alliance A011202 Clinical Trial. Alliance A011202临床试验纳入的新辅助化疗后残留淋巴结阳性乳腺癌患者中，腋窝清扫术对额外淋巴结病变和病理性淋巴结分期上调的影响因素讲者：Judy Boughey, Mayo Clinic, Rochester, Minnesota RF2-02: Axillary surgery after neoadjuvant systemic therapy (NST) for early-stage breast cancer – Treatment algorithms and prognostic impact of residual micrometastases in five neoadjuvant studies. 早期乳腺癌新辅助全身治疗（NST）后的腋窝手术——5项新辅助治疗研究中残留微转移的治疗路径和预后影响讲者：Johannes Holtschmidt, VP Medicine & Research GBG Forschungs GmbH RF2-03: Diagnostic performance of axillary ultrasound after neoadjuvant chemotherapy in initially node-positive breast cancer patients – results from the prospective AXSANA registry trial (NCT04373655). 初诊淋巴结阳性乳腺癌患者新辅助化疗后行腋窝超声的诊断效能——来自前瞻性AXSANA注册试验（NCT04373655）的结果讲者：Steffi Hartmann, University of Rostock, Rostock, Germany RF2-04: Ultrahypofractionated versus conventional fractionated sequential boost after whole-breast radiation therapy in breast cancer patients. One-year cosmetic outcomes of a randomized, controlled, phase 3 trial (ULTIMO). 乳腺癌患者全乳放疗后超大分割vs常规分割序贯加量疗效对比：一项随机、对照、3期试验（ULTIMO）1年美容效果讲者：Melanie Machiels, Universiteit Antwerpen, Antwerp, Belgium RF2-05: Validation of the association between TILs, ER status and benefit of radiotherapy in node positive, breast cancer patients: a DBCG study. DBCG研究：验证TILs、ER状态与淋巴结阳性乳腺癌患者放疗获益之间的关系讲者：Demet Özcan, Aarhus University Hospital, Aarhus, Denmark RF2-06: A Nationwide Double-Blind Phase III RCT Comparing Olanzapine and Prochlorperazine for Refractory Chemotherapy-Induced Nausea in NCORP Community Practices. 一项全国性、双盲、III期、随机对照试验（RCT），比较NCORP社区实践中奥氮平和丙氯拉嗪治疗化疗导致的难治性恶心讲者：Luke Peppone, University of Rochester Medical Center, Rochester, New York General Session 3 时间：12月13日9:00–11:45 am 地点：Hall 1 GS3-01: Circulating tumor DNA surveillance in ZEST, a randomized, phase 3, double-blind study of niraparib or placebo in patients w/ triple-negative breast cancer or HER2+ BRCA-mutated breast cancer with molecular residual disease after definitive therapy. ZEST是一项随机、3期、双盲研究，在尼拉帕利或安慰剂进行根治性治疗后有分子残留病变的三阴性乳腺癌或HER2+ BRCA突变乳腺癌患者中对循环肿瘤DNA进行监测。讲者：Nicholas Turner, Ralph Lauren Centre for Breast Cancer Research, London, United Kingdom GS3-03: Impact of Anthracyclines in High Genomic Risk Node-Negative HR+/HER2- Breast Cancer. 蒽环类药物对高基因组风险淋巴结阴性HR+/HER2-乳腺癌的影响讲者：Nan Chen, University of Chicago Medicine, Chicago, Illinois GS3-04: (Neo)adjuvant nab-PAC weekly vs sb-PAC q2w, followed by EC q2w, in genomically or clinically high-risk HR+/HER2- early breast cancer according to ET-response: final survival results from the WSG ADAPT-HR+/HER2- chemotherapy-trial. 在遗传或临床高危HR+/HER2-早期乳腺癌中，根据ET反应（新）辅助nab-PAC周疗 vs 每2周1次sb-PAC，随后每2周1次EC：WSG ADAPT-HR+/HER2-化疗试验最终生存结果讲者：Sherko Kuemmel, German Medical Institute, Berlin, Germany GS3-05: NSABP B-59/GBG-96-GeparDouze: A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy with atezolizumab or placebo followed by adjuvant atezolizumab or placebo in patients with Stage II and III triple-negative breast cancer. NSABP B-59/GBG-96-GeparDouze：一项针对II期和III期三阴性乳腺癌患者的随机双盲III期临床试验，比较新辅助化疗联合阿替利珠单抗或安慰剂，随后辅助使用阿替利珠单抗或安慰剂的效果讲者：Charles Geyer, University of Pittsburgh, Pittsburgh, Pennsylvania GS3-06: Neoadjuvant camrelizumab plus chemotherapy (chemo) for early or locally advanced triple-negative breast cancer (TNBC): a randomized, double-blind, phase 3 trial. 卡瑞利珠单抗联合化疗（chemo）新辅助治疗早期或局部晚期三阴性乳腺癌（TNBC）：一项随机、双盲、3期试验讲者：邵志敏（复旦大学附属肿瘤医院） GS3-08: In situ detection of individual classical MHC-I gene products in breast cancer identifies gene- and subtype-specific biased antigen presentation loss. 在乳腺癌中原位检测单个经典MHC-I基因产物，可识别出基因和亚型特异性的特异性抗原呈递缺失讲者：Paula Gonzalez-Ericsson, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee GS3-09: Multimodal integration of real world clinical and genomic data for the prediction of CDK4/6 inhibitors outcomes in patients with HR+/HER2- metastatic breast cancer. 真实世界临床和基因组数据的多模态整合用于预测CDK4/6抑制剂在HR+/HER2-转移性乳腺癌患者中的结局讲者：Enrico Moiso, Memorial Sloan Kettering Cancer Center, New York, New York GS3-10: Paired DNA and RNA analysis of CALGB 40603 (Alliance) reveals insights into the molecular and prognostic landscape of stage II-III triple-negative breast cancer. 配对的DNA和RNA分析CALGB 40603（Alliance）揭示了II-III期三阴性乳腺癌的分子和预后特征讲者：Brooke Felsheim, UNC School of Medicine, Chapel Hill, North Carolina Rapid Fire 3 时间：12月13日12:00 – 12:50 pm 地点：Hall 1 主持人：Peter Fasching, University Hospital Erlangen and Comprehensive Cancer Center Erlangen-EMN, Germany RF3-01: TBCRC 056: A phase II study of neoadjuvant niraparib with dostarlimab for patients with BRCA- or PALB2-mutated breast cancer: Results from the ER+/HER2- cohort. TBCRC 056研究ER+/HER2-队列的结果：一项尼拉帕利联合dostarlimab新辅助治疗BRCA突变或PALB2突变乳腺癌患者的II期研究讲者：Erica Mayer, Dana-Farber Cancer Institute, Boston, Massachusetts RF3-02: Efficacy of adjuvant avelumab by PD-L1, tumor infiltrating lymphocytes and residual cancer burden in high-risk triple negative breast cancer: secondary and exploratory endpoints of the phase III A-BRAVE trial. 基于PD-L1、肿瘤浸润淋巴细胞和残余肿瘤负荷对高危三阴性乳腺癌进行阿维鲁单抗辅助治疗的疗效：III期A-BRAVE研究的次要和探索性终点讲者：Maria Vittoria Dieci, University of Padua, Padua, Italy RF3-03: Nivolumab + Ipilimumab (NIVO+IPI) compared to capecitabine for triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy – Final results of BreastImmune-03, a multicenter randomized open-label phase II trial. 纳武利尤单抗+伊匹木单抗（NIVO+IPI）与卡培他滨在新辅助化疗后有残留病变的三阴性乳腺癌患者中的疗效比较——多中心随机开放标签II期试验BreastImmune-03的最终结果讲者：Olivier Trédan, Centre Lèon Bèrard, Lyon, France RF3-04: NRG-BR004: A Randomized, Double-blind, Phase III Trial of Taxane/Trastuzumab/Pertuzumab with Atezolizumab or Placebo in First-line HER2-positive Metastatic Breast Cancer. NRG-BR004：紫杉烷/曲妥珠单抗/帕妥珠单抗联合阿替利珠单抗或安慰剂一线治疗HER2阳性转移性乳腺癌的随机、双盲、III期试验讲者：Vicente Valero, MD Anderson Cancer Center, Houston, Texas RF3-05: A Phase 2 Study of Neoadjuvant HER2-targeted Therapy +/- Immunotherapy with Pembrolizumab (neoHIP). 新辅助HER2靶向治疗±帕博利珠单抗免疫治疗的2期研究（neoHIP）讲者：Heather McArthur, UT Southwestern Medical Center, Dallas, Texas RF3-06: Mepitel Film for the Reduction of Radiation Dermatitis in Post-mastectomy Radiation Therapy: Results from Alliance A221803: A Multicenter Phase III Randomized Clinical Trial Mepitel贴膜在减少乳腺癌术后放疗所致放射性皮炎中的应用：Alliance A221803多中心III期随机临床试验结果讲者：Kimberly Corbin, Mayo Clinic, Rochester, Minnesota RF3-07: ROSCO:Response to Optimal Selection of neoadjuvant Chemotherapy in Operable breast cancer: A randomised phase III, stratified biomarker trial of neoadjuvant 5-Fluorouracil, Epirubicin & Cyclophosphamide vs Docetaxel & Cyclophosphamide chemotherapy. ROSCO研究：随机III期、分层生物标志物试验，比较新辅助5-氟尿嘧啶、表柔比星与环磷酰胺vs多西他赛和环磷酰胺化疗方案，评估可手术乳腺癌新辅助化疗最优选择反应。讲者：Daniel Rea, University of Birmingham, Birmingham, United Kingdom Poster Spotlight Sessions ▌Concurrent Poster Spotlight Sessions 1, 3-5, 7 Session 1: New Insights into Immune Biomarkers（免疫生物标志物的新见解）时间：12月11日7:00 – 8:30 am 地点：Room 221ABC 主持人：David Rimm, Yale University Session 3: Highlights on Novel Therapeutics（新型治疗亮点）时间：12月11日7:00 – 8:30 am 地点：Stars at Night 1-2 主持人：Sara Tolaney, Dana-Farber Cancer Institute Session 4: Prediction of Chemotherapy Response（化疗疗效预测）时间：12月11日7:00 – 8:30 am 地点：Stars at Night 3-4 主持人：Sherene Loi, Peter Macallum Cancer Centre Session 5: The Heart of the Matter - Improving Adverse Effects（核心问题-改善不良反应）时间：12月11日7:00 – 8:30 am 地点：Hemisfair Ballroom 3 主持人：Anne Blaes, Masonic Cancer Center University of Minnesota Session 7: Targeting the ER and PI3K pathway: Novel drugs and combinations（靶向ER和PI3K通路：新型药物和组合）时间：12月11日7:00 – 8:30 am 地点：Hemisfair Ballroom 1-2 主持人：Shom Goel, Peter MacCallum Cancer Centre ▌Concurrent Poster Spotlight Sessions 2, 6, 8, 9 and 15 Session 2: Personalizing CDK 4/6 inhibitor therapy for patients with Metastatic Breast Cancer: Survival, QOL and biomarkers（转移性乳腺癌患者的个体化CDK 4/6抑制剂治疗：生存期、生活质量和生物标志物）时间：12月12日7:00 – 8:30 am 地点：Hemisfair Ballroom 1-2 主持人：Lisa Carey, Lineberger Comprehensive Cancer Center University of North Carolina Session 6: Locoregional Therapy（局部区域治疗）时间：12月12日7:00 – 8:30 am 地点：Room 221ABC 主持人：Mylin Torres, Winshop Cancer Institute of Emory University Session 8: Novel HER2 Therapeutics（新型HER2治疗）时间：12月12日7:00 – 8:30 am 地点：Stars at Night 1-2 主持人：Ian Krop, Yale School of Medicine Session 9: ctDNA uses for Minimal Residual Disease testing, tumor evolution, and novel technologies（ctDNA用于微小残留病检测、肿瘤进化和新技术）时间：12月12日7:00 – 8:30 am 地点：Stars at Night 3-4 主持人：Charles Perou, Lineberger Comprehensive Cancer Center University of North Carolina Session 15: Survivorship – Biomarker predictors and other survival-associated factors（生存-生物标志物预测和其他生存相关因素）时间：12月12日7:00 – 8:30 am 地点：Room 221ABC 主持人：Lindsay Peterson, Washington University Siteman Cancer Center, St. Louis, Missouri ▌Concurrent Poster Spotlight Sessions 10-14 Session 10: Addressing Racial Disparities in Breast Cancer Outcomes（探讨乳腺癌结局的种族差异）时间：12月13日7:00 – 8:30 am 地点：Hemisfair Ballroom 3 主持人：Yara Abdou, University of North Carolina School of Medicine Session 11: Imaging to Guide Breast Cancer Treatment – Molecular Imaging and AI（影像学指导乳腺癌治疗——分子影像学和人工智能）时间：12月13日7:00 – 8:30 am 地点：Hemisfair Ballroom 1-2 主持人：David Mankoff, Perelman School of Medicine University of Pennsylvania Session 12: Immunobiology Impact on Therapeutic Efficacy（免疫生物学对治疗效果的影响）时间：12月13日7:00 – 8:30 am 地点：Room 221ABC 主持人：Lajos Pusztai, Yale School of Medicine, New Haven, Connecticut Session 13: Molecular determinants of therapeutic response and resistance - Spotight on CDK 4/6i and ADCs （治疗反应和耐药的分子决定因素——聚焦CDK4/6i和ADCs）时间：12月13日7:00 – 8:30 am 地点：Stars at Night 1-2 主持人：Aditya Bardia, UCLA David Geffen School of Medicine, Los Angeles, California Session 14: Brain Metastasis（脑转移）时间：12月13日7:00–8:30 am 地点：Stars at Night 3-4 主持人：William Gradishar, Northwestern University Feinberg School of Medicine, Chicago, Illinois （来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床结果临床2期抗体药物偶联物

2024-10-12

·蒲公英Ouryao

FDA溶出方法数据库的特点分析

本文作者：曾文亮博士，迪哲医药CMCRA副总监 FDA溶出数据库可使用以下标准进行评价：剂型、仪器、旋转速度、溶出介质、取样时间点和特殊剂型的趋势。2015年7月，数据库中有1084种药品，其中超过50%为片剂。桨法（设备2）是数据库中最常见的设备，推荐用于488种产品（45%）。数据库中列出的转速对于设备1是35-200rpm，对于设备2是25-200rpm。114种方法推荐脱气或脱气水。最常引用的溶出介质的pH值在1-7.5的范围内；然而，几种溶出方法的pH值超出了生理范围（塞来昔布胶囊pH 1.2，格列本脲片剂pH 9.5，雷贝拉唑钠片剂pH 8.0，格列美脲片剂pH 7.8）。溶出曲线测试是在药品生命周期的不同阶段使用的最有用的方法之一：药物开发、稳定性研究、替代性评估、常规质量控制以及放大和批准后变更。该测试适用于多种剂型，如片剂和胶囊、透皮剂、内部使用和注射用混悬剂、栓剂、口香糖、咀嚼片、散剂、阴道插入物、植入物等。 FDA溶出度数据库(1)是开放访问的，每季度更新一次。检索时（2015年7月），数据库中有1084种药品。该数据库提供了药品的国际非专利名称（INN）、剂型、USP仪器类型、速度（rpm）、溶出介质、体积、取样时间点和最新更新日期等信息。该数据库是关于溶出度最易访问、最合适、最完整和信息最丰富的资源之一。本文是从剂型、仪器、转度和溶出介质方面对数据库进行简要综述。剂型 FDA数据库中最常见的剂型是片剂和胶囊（图1）。超过65%的产品为片剂剂型。有缓释片、包衣片、肠溶片、口腔崩解片（ODT）和咀嚼片。约26%的产品为胶囊，其中包括软胶囊、液体胶囊和缓释胶囊。图1:FDA溶出数据库中剂型统计 FDA数据库包含内服和外用、注射用混悬液的溶出方法悬浮液以及眼用和耳用悬浮液。然而，用于此类剂型的方法相当罕见(约占数据库内容的2.5%)。约2.5%的数据库描述了透皮剂型如贴剂、薄膜等的溶出。它还包含栓剂、散剂、丸剂、阴道环、阴道插入物、植入物、凝胶和口香糖的方法。仪器所有USP溶出仪器（设备1-7）都列在溶出方法数据库中。桨（设备2）是数据库中最常见的设备。推荐用于大约70%的溶出方法（图2），并被认为是速释固体剂型溶出曲线测试的首选仪器。对于胶囊剂型，可以使用沉降子来防止漂浮。它们包括螺旋、分叉和篮子下沉物。然而，锥体是桨叶的一个重要缺点。剂型的崩解物质可能沉降在搅拌速率最小的USP容器的底部，并形成捕获的药物颗粒的锥体，这导致低溶解速率。图2:FDA溶出数据库中桨法的使用频率大约17%的溶出方法（122种方法）推荐使用篮（设备1）。该装置通常用于溶出漂浮剂型。然而，它有几个缺点：分解的颗粒会堵塞篮子，小的分解的颗粒会掉出来。数据库中的三种缓释片推荐使用设备3（往复式圆筒）：马来酸氯苯那敏、马来酸右溴苯那敏、硫酸伪麻黄碱。在溶出测试程序中需要一个或多个pH/缓冲液变化的情况下，或者当流体动力学可以通过改变浸渍速率直接影响时，设备3可以特别有用。设备4（流通池）仅推荐用于三种方法：醋酸倍他米松/倍他米松磷酸钠注射用混悬液、醋酸甲羟孕酮注射用混悬液、醋酸甲泼尼龙注射用混悬液。设备5(盘上桨)用于局部和透皮剂型(盐酸丁丙诺啡/盐酸纳洛酮舌下膜、双氯芬酸依泊拉明局部贴剂、雌二醇透皮膜等)的溶出。设备6（旋转圆筒）被推荐用于七种方法，以确保局部和透皮药物产品的质量和性能。设备7(往复保持器)也用于透皮递送系统和各种剂型(例如，地塞米松的玻璃体内植入物)。 FDA数据库还提到了许多非药典设备，例如用于溶解药典中未描述的阴道环的培养箱振荡器。还有用于尼古丁口香糖分析的咀嚼机，欧洲药典对此有描述。对于254种产品（约23%），数据库没有说明试验条件，而是参考了相关的USP专论。许多药品没有提到方法，在这些情况下，需要进行方法开发，这对于注射剂型尤其重要。转速设备2（桨）的转速为25-200 rpm，如数据库中所列。最低值（25 rpm）通常用于混悬液（例如，氨苄西林用于口服混悬液，美洛昔康用于混悬液）。在双羟萘酸曲普瑞林注射用混悬液（200 rpm）和枸橼酸芬太尼锭剂（175 rpm）的溶出方法中列出了设备2的最快转速。典型的桨式搅拌速率为50rpm。设备1(篮)的转速值在35-200RPM的范围内变化。最常见的篮子转速是100 rpm（122种方法中的87种）。在富马酸喹硫平缓释片的溶出方法中，篮以最大速度（200 rpm）旋转。用于匹伐他汀钙片的设备1的最低速度为35 rpm，而用于雌二醇阴道片的最低速度推荐为40 rpm。设备5和6（分别为桨盘和旋转圆筒）最常见的速度是50rpm。用于装置4(流通池)的溶解介质的流速在8-17mL/min的范围内。溶出介质 FDA溶出数据库描述了大量不同的介质，从水或不同pH值的简单缓冲溶液到添加了表面活性剂、有机溶剂和酶的溶液。溶解介质的最简单选择是水。有114种方法推荐脱气或脱气水。水作为溶解介质的主要缺点是缓冲能力低。也不鼓励使用水作为溶出介质，因为pH和表面张力等测试条件可能因水源而异，并且在溶出测试本身期间可能由于活性和非活性成分的影响而发生变化。因此，当使用水作为介质时，在测试期间监测pH值是很重要的。然而，水仍然广泛用于溶出曲线测试（约10%的方法）。数据库中最常见的溶出介质的pH值范围为1-7.5（即1.2、2、4、4.5、5、6、6.8、7.2和7.5）。这些pH值存在于胃肠道中，被认为是生理相关的。值得注意的是，FDA数据库方法主要是为了确定药品的体外溶出曲线而开发的；因此，这些介质在某些情况下可能不反映体内生理状况。如今，该机构正在强调这种方法的区分力。它不必模拟体内发生的情况，但它必须对关键质量属性具有区分力。因此，FDA数据库描述了8种pH值超出生理参数范围的培养基（例如，塞来昔布胶囊的pH值为12，格列本脲片的pH值为9.5，雷贝拉唑钠片和盐酸氯胍片的pH值为8.0；格列美脲片、阿齐沙坦酯片、维a酸和异维a酸胶囊的pH值为7.8）。根据数据库，几种酸的水溶液可以用作溶出介质。最常用的酸性介质是以盐酸为基础的：0.1 М、0.01 М和0.001 М HCl。也可以使用磷酸(0.01 М)和其它酸性溶液。建议使用各种缓冲溶液（乙酸盐、柠檬酸盐和磷酸盐）在轻度低pH下进行溶出度测试。通过添加氢氧化钠溶液、硼酸盐缓冲液和Tris缓冲液来制备具有高pH值的溶出介质。对于水不溶性或微溶性药品（BCS II类或IV类），建议使用表面活性剂（数据床中有18.5%的方法），如十二烷基硫酸钠、吐温（聚山梨酯20和80）、十二烷基二甲胺氧化物（LDAO）、Triton X、Brij 35（聚氧乙烯月桂基醚）、十六烷基三甲基溴化铵（CTAB）等（图3）。最常用的表面活性剂是十二烷基硫酸钠（SLS，SDS）；据报道，其浓度范围为0.01-3%（图4）。溶出度是难溶性药物产品的吸收限制因素；因此，溶出度测试对于此类制剂特别有用。图3:FDA溶出数据库中常用的表面活性剂统计图4:FDA溶出数据库中常用的十二烷基硫酸钠浓度在某些特定情况下，建议使用有机化合物。例如，在阿托伐醌片剂的方法中使用含有40%异丙醇的介质。双羟萘酸曲普瑞林注射混悬液推荐使用含有5%甲醇的培养基。这些制剂中溶出度测试需要有机溶剂，这与阿托伐醌（<0.2 μ g/mL）和双羟萘酸曲普瑞林极低的水溶性有关。数据库中的溶出介质可能含有酶。例如，对于外层含有明胶的制剂(例如硬明胶和软明胶胶囊)，可以考虑添加酶。盐酸胃蛋白酶溶液用于度他雄胺、氯雷他定、双羟萘酸丙咪嗪、恩杂鲁胺和恩曲他滨胶囊的溶出。在溶出布洛芬、贝沙罗汀和盐酸伪麻黄碱胶囊的情况下，建议在溶出介质中加入胰酶。以模拟胃液（SGF）或模拟肠液（SIF）为溶出介质的方法有32种。在一些情况下，这些培养基可以含有酶。在FDA数据库的35个质量标准中，试验期间溶出介质pH值发生变化。对于溶出度测试必须模拟剂型在具有不同pH水平的GI部分之间的通过的产品和制剂（例如肠溶包衣片剂）是重要的。溶出介质的体积通常在500-1000 mL的范围内（图5）。最常用的体积是900 mL（56%的方法）、500 mL（12%的方法）和1000 mL（10%的方法）。在需要改变溶出介质pH的方法中，通常会出现750 mL和600 mL的体积。图5:FDA溶出数据库中常见的介质体积在特定情况下，FDA数据库建议体积小于500 mL（例如，双氯芬酸钾混悬液为400 mL）。溶出体积的降低通常是由增加定量测定方法的灵敏度和获得低剂量药物产品的溶出曲线的需要决定的。例如，数据库推荐设备1和设备2，其特别适用于剂量为0.1-1.2 mg的芬太尼口腔片剂和薄膜的小体积溶出介质(60-200mL)。 FDA数据库中的大多数溶出度测试应该在37±0.5℃下进行。如果溶出介质的温度不同于37℃，则规定溶出介质的温度。一般介质的温度应与产品应用部位的温度相同。局部剂型最常用的温度是32℃。在某些缓释剂型的情况下，产品将在施用部位停留很长时间，通常是几个月，如果测试温度大于37°C，则可以缩短溶出度测试的持续时间(7)。地塞米松植入物（玻璃体内）的试验温度为45°С，美沙拉秦栓剂为40°С，丙氯拉嗪直肠栓剂为38°С。溶解介质的温度也可以低于32℃。例如，硝唑尼特的口服混悬液和片剂以及棕榈酸帕利哌酮的注射混悬液为25°C。取样时间点应进行取样以获得完整的溶出曲线。对于速释产品，FDA数据库中的最小采样时间点数为3个（例如，利培酮口腔崩解片为5、10、15分钟）。然而，通常使用五个或更多个点（例如，59种方法中的10、20、30、45和60分钟；43种方法中的5、10、15、20和30分钟；25种方法中的10、15、20、30和45分钟；12种方法中的15、30、45、60和90分钟）。速释剂型最常用的采样时间点为10分钟（69%的方法）、20分钟（60%的方法）、30分钟（69%的方法）和45分钟（53%的方法）。较少使用的时间点是15分钟（37%的方法）、60分钟（25%的方法）等。 FDA数据库中的大多数方法要求在10分钟（319种方法）、5分钟（210种方法）或15分钟（48种方法）内开始取样。对于口腔崩解片剂，通常提前开始取样（2或3分钟）。数据库要求舌下剂型在1或2分钟开始取样。整个采样过程通常需要30至60分钟，但有时可能需要15分钟或180分钟或更长时间。缓释产品的取样时间应单独考虑，通常从0.5或1小时开始，从4至24小时开始，包括5-12个时间点。在最困难的情况下，溶出可持续96小时（盐酸纳曲酮胶囊、格拉司琼透皮膜）、240小时（地塞米松植入物）、使用眼眶振荡器（醋酸戈舍瑞林植入物，10.8 mg规格）的84天，使用培养箱振荡器（雌二醇阴道环）的45天。特殊剂型溶出曲线测试适用于各种新型或特殊剂型。这样的剂型在FDA溶出度数据库中通过口腔崩解片剂(ODT)、混悬剂以及局部和透皮递送系统来表示。可以注意到特殊剂型溶出曲线测试的一些重要特征。旋转桨法是ODT最常用的方法。有19种使用桨的ODT溶出方法和3种使用篮法。这些方法的一个显著特征是早期的第一采样点；它通常小于10分钟（通常为2-5分钟）。 25%的悬浮液药物释放试验方法推荐使用低搅拌速率（25-30 rpm）的旋转桨。此外，使用脱气水作为溶解介质相对频繁（16%的悬浮方法）。推荐使用盘上桨和旋转圆筒测试透皮剂型（约50/50）。这些方法的一个重要特征是介质pH值范围为4.5至6.8，反映了生理皮肤状况。出于同样的原因，测试温度通常设置为32℃(8)。结论 FDA溶出方法数据库可以作为溶出度测试各个方面的最新信息来源：仪器、溶出介质、旋转速度、测试条件和采样时间点。该数据库对于仿制药产品的溶出曲线测试特别有用。该数据库的一些最重要的优势是每季度更新、开放访问、数据系统化和易于使用。应该强调的是，数据库是溶出曲线测试的起点，如果有适当的理由，也可以使用其他条件。参考文献：略作者精彩原创集锦 1、创新药研发中原料药工艺与沟通交流常见难点 2、创新药研发中「制剂工」常见难点 3、创新药研发中「变更」相关难点 4、创新药研发中「质量分析控制」相关难点（1） 5、创新药研发中「质量分析控制」相关难点（2） 6、创新药研发难点分析与CMC研究策略探讨 7、《已上市化学药品药学变更研究技术指导原则（试行）原料药变更的问答》浅析 8、FDA：原料药中亚硝胺风险评估的最新观点 9、亚硝胺「传奇」：5年来监管和制药界的反思 10、【学习笔记】2023年度CDE审评报告 11、FDA审评：吡托布鲁替尼的药学变更桥接(完) 12、CDE：ICH指南在国内的实施概况 13、「解读」FDA审评：repotrectinib胶囊5次CMC会议内容 14、FDA：IND阶段CMC关注点 15、药品注册检验难点与建议曾文亮博士迪哲医药CMCRA副总监，公众号“文亮频道”主理人。山东大学本科与硕士，上海中医药大学博士。近20年药物研发经验，擅长新药研发与注册申报，近5年积累了近十个小分子新药中美IND申报成功和两个1类抗肿瘤新药上市申报成功经验。先后任职于某大型CRO医药研发公司、USP大中华区研发中心和港资原料药厂等，主导过MNC质量研究项目、USP各论更新和药厂QC实验室通过国家GMP检查和WHO审计。受中国医药保健品进出口商会邀请在二十二届世界制药原料药中国展（CPHI）主导策划了“小分子创新药质量研究和注册策略”沙龙并发表主题演讲；同时受专业药学论坛邀请发表了《创新药质量研究要点和案例分析》、《中美新药申报沟通交流常见问题和案例分析》、《亚硝胺杂质的FDA和EMA控制策略》、《分析方法开发，验证和转移的统计学评价》和《FDA483中清洁验证的典型案例分析》等十余次主题演讲。更多精彩内容可关注： ▲ 关注文亮频道，探索未知世界

医药出海一致性评价

2024-09-23

·Business Wire

Avenacy to Share Company’s Year One Progress at CPHI Milan 2024

SCHAUMBURG, Ill.--( BUSINESS WIRE )--Avenacy, a specialty pharmaceutical company focused on supplying critical medications, looks forward to celebrating its first year of growth and success since launching in October 2023. Backed by a robust global network of development and FDA-inspected contract manufacturing partners, Avenacy has already brought 13 injectable products to the U.S. market to address key gaps in the drug supply chain. “We are incredibly proud of the achievements and progress we have made at Avenacy since launching nearly a year ago as a trusted partner and provider of critical injectable medicines for the U.S. healthcare system,” said Jeff Yordon, Co-Founder and CEO of Avenacy. “We have acted swiftly and decisively to bring over a dozen medications to the U.S. market to help meet the needs of patients, strengthened our financial position with the addition of esteemed pharmaceutical investor and businessman, Dr. Patrick Soon-Shiong, and built out our infrastructure and leadership to support scaling up our business. As we look to usher in the next phase of growth for Avenacy, we will remain steadfast in our goal of enhancing patient care and enabling access to safe, high-quality essential medications.” Through a rigorous and optimized selection process, Avenacy has launched thirteen products in the U.S. market, including: Melphalan Hydrochloride for Injection Bivalirudin for Injection Fosaprepitant for Injection Fulvestrant Injection Furosemide for Injection Desmopressin Acetate for Injection Eptifibatide for Injection Magnesium Sulfate in Water for Injection Isoproterenol Hydrochloride Injection, USP Tranexamic Acid Injection, USP Prochlorperazine Edisylate Injection, USP Palonosetron Hydrochloride Injection, USP Metoclopramide Injection, USP The Company is well-positioned to continue expanding its differentiated portfolio to meet the needs of today’s dynamic drug supply chain while ensuring quality of care to patients. All of Avenacy’s products feature unique packaging and labeling designed to assist healthcare providers with accurate medication selection, thereby supporting a reduction in administration errors and improper dosing. The Company also utilizes ready-to-use formulations of essential medications to help address dosing inaccuracies, enhance patient safety, and streamline efficiency – all with the ultimate goal of improving patient care. Avenacy will be sharing its first year progress, differentiated business model, and diverse partner network at this year’s CPHI 2024 Conference, taking place in Milan from October 8-10. During this time, the Company will be hosting meetings with potential partners, customers, and investors, as it seeks to expand its global presence and portfolio of critical injectable medicines. About Avenacy Avenacy is a U.S.-based specialty pharmaceutical company focused on supplying critical injectable medications used to treat patients in various medically supervised settings, from acute care hospitals to outpatient clinics and physician offices. Through a rigorous and optimized selection process, the Company is building out a pipeline of high-quality FDA approved injectable products in order to ensure a resilient portfolio that can meet the needs of today’s dynamic drug supply chain. With an experienced team, commitment to quality and reliability, and product offerings intended to facilitate safe and efficient patient care, Avenacy strives to be a trusted partner for essential medications. Avenacy was launched in 2023 and is headquartered in Schaumburg, IL. For more information, please visit http://www.avenacy.com/ .

高管变更

100 项与丙氯拉嗪相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00493	丙氯拉嗪	N05AB04	DB00433

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
精神分裂症	美国	GlaxoSmithKline, Inc.	1959-01-26

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临床结果

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分期

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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


NCT03185130 (I-FiBH, CTgov)	临床4期	头痛	58	Prochlorperazine 0.15 mg/kg up to 10 mg IV+Normal Saline 5mL+Diphenhydramine 1 mg/kg up to 50 mg IV (Standard Treatment Arm)	簾蓋鹹憲觸簾餘膚廠廠(獵繭壓鹽鹹觸膚糧夢齋) = 憲製蓋鹽簾積願襯網齋願廠醖製觸獵衊窪構築 (夢獵簾觸鹽壓鹹齋選築, 淵夢築膚衊鏇壓廠顧艱 ~ 遞積願襯壓鹹繭簾衊窪) 更多	-	2024-06-06
				Normal Saline 20mL/kg+Prochlorperazine 0.15 mg/kg up to 10 mg IV+Diphenhydramine 1 mg/kg up to 50 mg IV (Study Arm)	簾蓋鹹憲觸簾餘膚廠廠(獵繭壓鹽鹹觸膚糧夢齋) = 夢鏇獵餘鹽憲糧製餘壓願廠醖製觸獵衊窪構築 (夢獵簾觸鹽壓鹹齋選築, 憲網襯鏇衊廠築觸蓋遞 ~ 夢淵鬱構鬱範壓鹽繭簾) 更多
NCT03435003 (CTgov)	临床4期	术后恶心呕吐 \| 呕吐	83	dexmedetomidine+Compazine+Total intravenous anesthesia+scopolamine transdermal+sugammadex+Reglan+Propofol+Fentanyl+Ondansetron+Aprepitant 80 mg Oral Capsule+Dexamethasone (Intervention Arm)	壓衊遞積齋構膚鬱膚夢(繭廠繭糧願願鏇顧鏇窪) = 糧積選顧繭鏇糧鬱顧繭製簾簾窪鏇憲鹽艱餘鹹 (選蓋觸鏇衊窪簾艱鏇憲, 淵鹽遞窪遞簾積齋衊壓 ~ 願廠艱築醖網繭獵衊顧) 更多	-	2024-02-14
				Compazine+sugammadex+Reglan+Sevoflurane+Desflurane+Ondansetron+Dexamethasone (Control Arm)	壓衊遞積齋構膚鬱膚夢(繭廠繭糧願願鏇顧鏇窪) = 獵窪衊淵範顧鏇淵糧鹽製簾簾窪鏇憲鹽艱餘鹹 (選蓋觸鏇衊窪簾艱鏇憲, 艱鑰獵繭夢衊憲鑰鹽衊 ~ 淵衊網壓鏇衊壓簾膚願) 更多
CNS2023	临床1/2期	偏头痛	17	Normal Saline, Prochlorperazine, Ketorolac	蓋願鏇製蓋憲構繭醖醖(餘鑰艱鑰積構築觸鹽鑰) = 糧選憲範積獵淵醖築齋憲顧顧衊壓鹹鬱築膚顧 (窪壓積膚膚願夢選衊獵 ) 更多	积极	2023-10-01
NCT01629329 (Migraine, CTgov)	临床4期	急性偏头痛	93	Aspirin, Acetaminophen, Caffeine pills (Aspirin, Acetaminophen, Caffeine Pills)	繭壓鏇餘醖壓獵選選簾(蓋淵蓋顧願夢襯窪艱顧) = 繭齋夢廠窪構構築網構襯繭襯選餘蓋願蓋繭窪 (範醖襯齋齋積顧憲淵艱, 夢齋醖網憲觸憲襯製選 ~ 餘壓獵顧鏇繭鬱獵願鏇) 更多	-	2020-03-18
				Prochlorperazine 10mg (Prochlorperazine 10mg)	繭壓鏇餘醖壓獵選選簾(蓋淵蓋顧願夢襯窪艱顧) = 範範鏇選淵獵鬱遞選鏇襯繭襯選餘蓋願蓋繭窪 (範醖襯齋齋積顧憲淵艱, 願觸鹽觸憲夢鹽齋範積 ~ 繭夢糧鏇膚齋鏇鹽壓繭) 更多
NCT02389829 (CTgov)	临床4期	急性偏头痛	127	Hydromorphone (Hydromorphone)	顧夢繭鏇膚夢網壓製艱(製鏇鹽鑰糧積窪獵獵顧) = 襯願壓淵積夢糧鹹憲艱選齋壓窪糧觸構夢遞壓 (選蓋蓋膚構膚繭網襯憲, 衊鹽齋餘衊蓋鹹獵衊範 ~ 壓製範餘襯醖選鬱餘範) 更多	-	2018-06-06
				prochlorperazine+Diphenhydramine (Prochlorperazine)	顧夢繭鏇膚夢網壓製艱(製鏇鹽鑰糧積窪獵獵顧) = 衊遞鑰範壓範窪廠簾憲選齋壓窪糧觸構夢遞壓 (選蓋蓋膚構膚繭網襯憲, 鹽衊積夢築簾選餘獵觸 ~ 餘選艱壓獵憲艱膚蓋築) 更多
NCT00422812 (CTgov)	临床2期	先兆偏头痛	400	Inhaled Placebo (Inhaled Placebo)	製壓餘獵積簾廠鹽構鬱(鹹鏇遞範鏇鏇遞鹹鹹鬱) = 淵鑰網鏇遞鑰餘醖鏇網範憲窪遞醖壓選餘觸構 (獵鬱簾窪醖繭獵壓窪觸, 壓網壓顧壓壓醖觸衊鏇 ~ 觸積蓋顧製襯襯獵獵鹹) 更多	-	2018-01-25
				Prochlorperazine+Staccato (Inhaled PCZ 5 mg)	製壓餘獵積簾廠鹽構鬱(鹹鏇遞範鏇鏇遞鹹鹹鬱) = 構廠選顧廠選膚簾廠遞範憲窪遞醖壓選餘觸構 (獵鬱簾窪醖繭獵壓窪觸, 衊醖齋壓壓壓淵糧憲憲 ~ 鹹鑰範範構衊醖範廠網) 更多
NCT00590317 (CTgov)	临床2期	恶心 \| 恶心和呕吐 \| 呕吐	64	Prochlorperazine (Prochlorperazine)	繭積製襯積願蓋醖艱鏇(構艱鹽鏇夢築廠廠積鹽) = 顧鏇蓋襯獵築製築觸艱築夢醖簾願窪築糧襯觸 (鑰築鹽選鹽廠襯選簾艱, 膚糧艱簾窪壓糧鹽憲簾 ~ 淵鏇鏇鹹糧構積憲築簾) 更多	-	2014-05-19
				Ondansetron (Ondansetron)	繭積製襯積願蓋醖艱鏇(構艱鹽鏇夢築廠廠積鹽) = 餘憲廠範選簾襯選膚繭築夢醖簾願窪築糧襯觸 (鑰築鹽選鹽廠襯選簾艱, 蓋衊觸製廠鹽齋窪憲獵 ~ 鏇夢網窪構鹽願觸構窪) 更多
NCT00475085 (CTgov)	临床3期	恶心 \| 延迟性恶心和呕吐	1,021	prochlorperazine+placebo+granisetron hydrochloride+Dexamethasone (Arm II)	膚襯夢夢願艱築膚窪鹹(夢鹹選鬱簾選鑰餘積築) = 膚餘夢鏇壓遞襯鹹襯鏇觸蓋襯顧壓獵餘構遞觸 (襯選淵鹹淵遞顧膚襯繭, 繭範衊齋餘鏇鹽齋鏇觸 ~ 鹽膚鏇範襯醖築遞製製) 更多	-	2013-11-03
				placebo+palonosetron hydrochloride+aprepitant+Dexamethasone (Arm III)	膚襯夢夢願艱築膚窪鹹(夢鹹選鬱簾選鑰餘積築) = 鬱選鏇齋艱製餘糧襯壓觸蓋襯顧壓獵餘構遞觸 (襯選淵鹹淵遞顧膚襯繭, 積壓選壓願艱遞鏇憲積 ~ 簾積鑰鹹鑰築顧遞選醖) 更多
ASCO2010	N/A	化疗引起的恶心和呕吐	96	Prochlorperazine	餘齋鹽製窪製構憲簾鏇(遞艱餘夢齋鏇選衊襯鏇) = 鏇構衊齋廠鏇憲齋顧遞觸鏇壓顧構築鹽艱鏇鬱 (齋夢廠願積醖鑰醖構憲 )	-	2010-05-20
				5HT3 antagonists	餘齋鹽製窪製構憲簾鏇(遞艱餘夢齋鏇選衊襯鏇) = 鹹夢網淵鹹膚構構壓簾觸鏇壓顧構築鹽艱鏇鬱 (齋夢廠願積醖鑰醖構憲 )
NCT02657031 \| NCT03185130 (Pubmed \| Ann Emerg Med)	临床4期	急性偏头痛	77	Metoclopramide 20 mg	衊膚遞淵網憲襯憲夢積(鹽膚獵範獵觸獵願襯鬱) = 糧壓觸膚築顧願鬱鏇廠願簾遞襯選淵築壓廠廠 (積製廠齋鏇糧鑰範艱醖 )	-	2008-10-01