midazolam (BioDeep_00000405904)
Main id: BioDeep_00000002073
natural product
代谢物信息卡片
化学式: C18H13ClFN3 (325.0782)
中文名称: 咪达唑仑
谱图信息:
最多检出来源 () 0%
分子结构信息
SMILES: CC1=NC=C2N1C3=C(C=C(C=C3)Cl)C(=NC2)C4=CC=CC=C4F
InChI: InChI=1S/C18H13ClFN3/c1-11-21-9-13-10-22-18(14-4-2-3-5-16(14)20)15-8-12(19)6-7-17(15)23(11)13/h2-9H,10H2,1H3
描述信息
D002491 - Central Nervous System Agents > D002492 - Central Nervous System Depressants > D006993 - Hypnotics and Sedatives
D002491 - Central Nervous System Agents > D002492 - Central Nervous System Depressants > D000777 - Anesthetics
N - Nervous system > N05 - Psycholeptics > N05C - Hypnotics and sedatives > N05CD - Benzodiazepine derivatives
D002492 - Central Nervous System Depressants > D014149 - Tranquilizing Agents > D014151 - Anti-Anxiety Agents
D002491 - Central Nervous System Agents > D011619 - Psychotropic Drugs > D014149 - Tranquilizing Agents
C78272 - Agent Affecting Nervous System > C29756 - Sedative and Hypnotic > C1012 - Benzodiazepine
D018377 - Neurotransmitter Agents > D018682 - GABA Agents > D018757 - GABA Modulators
COVID info from clinicaltrial, clinicaltrials, clinical trial, clinical trials
C78272 - Agent Affecting Nervous System > C28197 - Antianxiety Agent
Corona-virus
Coronavirus
SARS-CoV-2
COVID-19
SARS-CoV
COVID19
SARS2
SARS
同义名列表
数据库引用编号
22 个数据库交叉引用编号
- ChEBI: CHEBI:6931
- KEGG: C07524
- KEGGdrug: D00550
- PubChem: 4192
- DrugBank: DB00683
- ChEMBL: CHEMBL655
- MeSH: Midazolam
- CAS: 59467-64-0
- MoNA: WA001079
- MoNA: WA001078
- MoNA: WA001077
- MoNA: WA001076
- MoNA: WA001075
- MoNA: CCMSLIB00004679251
- MoNA: FiehnHILIC002103
- MoNA: FiehnHILIC000530
- PubChem: 9727
- CAS: 59467-70-8
- PDB-CCD: 08J
- NIKKAJI: J31.859K
- RefMet: Midazolam
- KNApSAcK: 6931
分类词条
相关代谢途径
Reactome(0)
BioCyc(0)
PlantCyc(0)
代谢反应
0 个相关的代谢反应过程信息。
Reactome(0)
BioCyc(0)
WikiPathways(0)
Plant Reactome(0)
INOH(0)
PlantCyc(0)
COVID-19 Disease Map(0)
PathBank(0)
PharmGKB(0)
0 个相关的物种来源信息
在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有:
- PubMed: 来源于PubMed文献库中的文献信息,我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表,这个列表按照代谢物同时出现的文献数量降序排序,取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
- NCBI Taxonomy: 通过文献数据挖掘,得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序,取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
- Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
- Chemical Reaction: 在化学反应过程中,存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。
点击图上的相关代谢物的名称,可以跳转到相关代谢物的信息页面。
文献列表
- Cuitong Wang, Bin Cheng, Wei Wei, Lanlan Gui, Wushuang Zeng, Yutong Wang, Yixuan Wang, Qi Chen, Liang Xu, Jia Miao, Ke Lan. Comparison of 1Beta- and 5Beta-hydroxylation of Deoxycholate and Glycodeoxycholate as In Vitro Index Reactions for Cytochrome P450 3A Activities.
Drug metabolism and disposition: the biological fate of chemicals.
2024 Jan; 52(2):126-134. doi:
10.1124/dmd.123.001513
. [PMID: 38050044] - Sumit Bansal, C Austin Zamarripa, Tory R Spindle, Elise M Weerts, Kenneth E Thummel, Ryan Vandrey, Mary F Paine, Jashvant D Unadkat. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants.
Clinical pharmacology and therapeutics.
2023 Jun; ?(?):. doi:
10.1002/cpt.2973
. [PMID: 37313955] - Rakshit S Tanna, James T Nguyen, Deena L Hadi, Matthew E Layton, John R White, Nadja B Cech, Nicholas H Oberlies, Allan E Rettie, Kenneth E Thummel, Mary F Paine. Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom.
Clinical pharmacology and therapeutics.
2023 Mar; ?(?):. doi:
10.1002/cpt.2891
. [PMID: 36924284] - Xiao-Ling Zhu, Hui-Wen Zhang, Wen-Jing Peng, Shan Gao, Zhi-Lai Yang, Ji-Qian Zhang, Xue-Sheng Liu. Autophagy impairment is involved in midazolam-induced lipid droplet accumulation and consequent phagocytosis decrease in BV2 cells.
Biochemical and biophysical research communications.
2023 Feb; 643(?):147-156. doi:
10.1016/j.bbrc.2022.12.067
. [PMID: 36609155] - Jian Liu, Yu-Jun Ye, Shu-Min Liu, Shuang Liu. [Analysis of the effect of midazolam on pain in a rat model of lumbar disc herniation based on the p38 MAPK signaling pathway].
Zhongguo gu shang = China journal of orthopaedics and traumatology.
2023 Jan; 36(1):55-60. doi:
10.12200/j.issn.1003-0034.2023.01.010
. [PMID: 36653007] - Feyza Çalışır, Aykut Urfalıoğlu, Bora Bilal, Abdullah Tok, Hasan Alperen Bolcal, Hafize Öksüz. The effect of lavender aromatherapy on the level of intraoperative anxiety in caesarean case under spinal anesthesia: A randomized controlled trial.
Explore (New York, N.Y.).
2022 Dec; ?(?):. doi:
10.1016/j.explore.2022.11.008
. [PMID: 36476355] - Yusheng Yao, Jinsheng Guan, Linwei Liu, Bingbing Fu, Lei Chen, Xiaochun Zheng. Discharge readiness after remimazolam versus propofol for colonoscopy: A randomised, double-blind trial.
European journal of anaesthesiology.
2022 12; 39(12):911-917. doi:
10.1097/eja.0000000000001715
. [PMID: 35796575] - Hui-Lin Yang, Ying Li, Yi Chen, Si-Ying Chen, Yue-Ting Li, Yong Huang, Lin Zheng, Jing Huang, Yong-Lin Wang, Zi-Peng Gong. [Effect of Laportea bulbifera extract on CYP450 enzyme activities in rats by Cocktail probe drug method].
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica.
2022 Dec; 47(23):6320-6332. doi:
10.19540/j.cnki.cjcmm.20220623.204
. [PMID: 36604876] - Nana Chi, Longfei Chen, Yongmei Sheng, Wenwen Song, Fanqing Meng, Yang Yang. Effect of midazolam on cerebral oxygen metabolism in patients with cerebral infarction.
Panminerva medica.
2022 09; 64(3):400-401. doi:
10.23736/s0031-0808.20.04224-x
. [PMID: 33528150] - Yu-Peng Qi, Wen-Jing Ma, Ying-Ya Cao, Qun Chen, Qian-Cheng Xu, Shi Xiao, Wei-Hua Lu, Zhen Wang. Effect of Dexmedetomidine on Intestinal Barrier in Patients Undergoing Gastrointestinal Surgery-A Single-Center Randomized Clinical Trial.
The Journal of surgical research.
2022 09; 277(?):181-188. doi:
10.1016/j.jss.2022.03.031
. [PMID: 35500513] - Kine Eide Kvitne, Kristine Hole, Veronica Krogstad, Birgit Malene Wollmann, Christine Wegler, Line K Johnson, Jens K Hertel, Per Artursson, Cecilia Karlsson, Shalini Andersson, Tommy B Andersson, Rune Sandbu, Jøran Hjelmesæth, Eva Skovlund, Hege Christensen, Rasmus Jansson-Löfmark, Anders Åsberg, Espen Molden, Ida Robertsen. Correlations between 4β-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range.
European journal of clinical pharmacology.
2022 Aug; 78(8):1289-1299. doi:
10.1007/s00228-022-03336-9
. [PMID: 35648149] - Hiromi Matsuda, Jungo Takenaka, Mariko Kawabata, Toshiaki Komatsu, Kazumi Sakanoue, Koichiro Atsuda, Hirotsugu Okamoto. Serum concentration of oral midazolam as pediatric preanesthetic medication and factors related to the sedation level.
Acta anaesthesiologica Scandinavica.
2022 Aug; 66(7):818-822. doi:
10.1111/aas.14077
. [PMID: 35488482] - R A Gray, D J Heal, D R Maguire, L R Gerak, M A Javors, S Smith, C P France. Preclinical Assessment of the Abuse Potential of Purified Botanical Cannabidiol: Self-Administration, Drug Discrimination, and Physical Dependence.
The Journal of pharmacology and experimental therapeutics.
2022 Jul; 382(1):54-65. doi:
10.1124/jpet.121.000988
. [PMID: 35489780] - Seok Hwee Koo, Gaik Hong Soon, Alain Pruvost, Henri Benech, Tiing Leong Ang, Edmund Jon Deoon Lee, Daphne Shih Wen Ang. Evaluation of a six-probe cocktail (caffeine, tolbutamide, omeprazole, dextromethorphan, midazolam, and digoxin) approach to estimate hepatic drug detoxification capability and dosage requirements after a single oral dosing in healthy Chinese volunteers.
Naunyn-Schmiedeberg's archives of pharmacology.
2022 07; 395(7):815-826. doi:
10.1007/s00210-022-02235-1
. [PMID: 35394133] - Urs Duthaler, Fabio Bachmann, Claudia Suenderhauf, Tanja Grandinetti, Florian Pfefferkorn, Manuel Haschke, Petr Hruz, Jamal Bouitbir, Stephan Krähenbühl. Liver Cirrhosis Affects the Pharmacokinetics of the Six Substrates of the Basel Phenotyping Cocktail Differently.
Clinical pharmacokinetics.
2022 07; 61(7):1039-1055. doi:
10.1007/s40262-022-01119-0
. [PMID: 35570253] - Tim J L Smeets, Abraham J Valkenburg, Mathieu van der Jagt, Birgit C P Koch, Henrik Endeman, Diederik A M P J Gommers, Sebastian D T Sassen, Nicole G M Hunfeld. Hyperinflammation Reduces Midazolam Metabolism in Critically Ill Adults with COVID-19.
Clinical pharmacokinetics.
2022 07; 61(7):973-983. doi:
10.1007/s40262-022-01122-5
. [PMID: 35397768] - Dagmar Kubitza, Michael Heckmann, Jana Distler, Annemone Koechel, Stephan Schwers, Friederike Kanefendt. Pharmacokinetics, pharmacodynamics and safety of BAY 2433334, a novel activated factor XI inhibitor, in healthy volunteers: A randomized phase 1 multiple-dose study.
British journal of clinical pharmacology.
2022 07; 88(7):3447-3462. doi:
10.1111/bcp.15230
. [PMID: 35014061] - Ilia G Denisov, Yelena V Grinkova, Mark A McLean, Tyler Camp, Stephen G Sligar. Midazolam as a Probe for Heterotropic Drug-Drug Interactions Mediated by CYP3A4.
Biomolecules.
2022 06; 12(6):. doi:
10.3390/biom12060853
. [PMID: 35740978] - Matthias Hoch, Tirtha Sengupta, Florence Hourcade-Potelleret. Pharmacokinetic drug interactions of asciminib with the sensitive cytochrome P450 probe substrates midazolam, warfarin, and repaglinide in healthy participants.
Clinical and translational science.
2022 06; 15(6):1406-1416. doi:
10.1111/cts.13252
. [PMID: 35293131] - Juyan Zheng, Wei Zhang, PeiPei Kang, Xiaojiao Zheng, Kai He, Hong Bai, Xuerong Yu. Midazolam Ameliorates Impairment of the Blood-Brain Barrier (BBB) Against LPS.
Neurotoxicity research.
2022 Jun; 40(3):751-762. doi:
10.1007/s12640-022-00508-4
. [PMID: 35451708] - QingLiang Wu, YiTing Hu, CuiTong Wang, Wei Wei, LanLan Gui, WuShuang Zeng, Changxiao Liu, Wei Jia, Jia Miao, Ke Lan. Reevaluate In Vitro CYP3A Index Reactions of Benzodiazepines and Steroids between Humans and Dogs.
Drug metabolism and disposition: the biological fate of chemicals.
2022 06; 50(6):741-749. doi:
10.1124/dmd.122.000864
. [PMID: 35351776] - Yifan Bao, Mi Phan, Junjie Zhu, Xiaochao Ma, José E Manautou, Xiao-Bo Zhong. Alterations of Cytochrome P450-Mediated Drug Metabolism during Liver Repair and Regeneration after Acetaminophen-Induced Liver Injury in Mice.
Drug metabolism and disposition: the biological fate of chemicals.
2022 05; 50(5):694-703. doi:
10.1124/dmd.121.000459
. [PMID: 34348940] - Odette O, Bradley T Simon, Lisa S Ebner, Ignacio Lizarraga, Xiaocun Sun, Sherry K Cox. The pharmacokinetics and pharmacodynamics of midazolam after intravenous administration to donkeys (Equus africanus asinus).
Canadian journal of veterinary research = Revue canadienne de recherche veterinaire.
2022 04; 86(2):125-131. doi:
. [PMID: 35388227]
- Yukino Oshima, Makoto Sano, Ichie Kajiwara, Yoshimi Ichimaru, Tomoaki Itaya, Tomoya Kuramochi, Emiko Hayashi, Jinsuk Kim, Osamu Kitajima, Yohei Masugi, Atsushi Masamune, Hideaki Ijichi, Yukimoto Ishii, Takahiro Suzuki. Midazolam exhibits antitumour and anti-inflammatory effects in a mouse model of pancreatic ductal adenocarcinoma.
British journal of anaesthesia.
2022 Apr; 128(4):679-690. doi:
10.1016/j.bja.2021.12.042
. [PMID: 35120712] - Kimberly N Shudofsky, Paddy K C Janssen, Norbert Foudraine, Jos L M L le Noble. Clearance of Lormetazepam, Midazolam, and Their Conjugated Metabolites by Continuous Venovenous Hemofiltration During Prolonged Sedation in Critically Ill Patients With COVID-19-Associated Acute Respiratory Distress Syndrome.
Journal of clinical pharmacology.
2022 04; 62(4):568-570. doi:
10.1002/jcph.2005
. [PMID: 34793610] - Mizuho Tashiro, Atsushi Tohei. Recommended doses of medetomidine-midazolam-butorphanol with atipamezole for preventing hypothermia in mice.
The Journal of veterinary medical science.
2022 Mar; 84(3):445-453. doi:
10.1292/jvms.21-0479
. [PMID: 35135936] - Felix Stader, Manuel Battegay, Parham Sendi, Catia Marzolini. Physiologically Based Pharmacokinetic Modelling to Investigate the Impact of the Cytokine Storm on CYP3A Drug Pharmacokinetics in COVID-19 Patients.
Clinical pharmacology and therapeutics.
2022 03; 111(3):579-584. doi:
10.1002/cpt.2402
. [PMID: 34496043] - Stephan Schaller, Frederico S Martins, Pavel Balazki, Sonja Böhm, Joachim Baumgart, Ralf A Hilger, Dietrich W Beelen, Claudia Hemmelmann, Arne Ring. Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach.
British journal of clinical pharmacology.
2022 02; 88(4):1722-1734. doi:
10.1111/bcp.15081
. [PMID: 34519068] - Lujing Wang, Yang Chen, Wangda Zhou, Xin Miao, Honghui Zhou. Utilization of physiologically-based pharmacokinetic model to assess disease-mediated therapeutic protein-disease-drug interaction in immune-mediated inflammatory diseases.
Clinical and translational science.
2022 02; 15(2):464-476. doi:
10.1111/cts.13164
. [PMID: 34581012] - Song Ren, Karthick Vishwanathan, Mireille Cantarini, Paul Frewer, Indira Hara, Graeme Scarfe, Wendy Burke, Stein Schalkwijk, Yan Li, David Han, Ronald Goldwater. Clinical evaluation of the potential drug-drug interactions of savolitinib: Interaction with rifampicin, itraconazole, famotidine or midazolam.
British journal of clinical pharmacology.
2022 02; 88(2):655-668. doi:
10.1111/bcp.14994
. [PMID: 34322894] - Jae-Ah Seo, Nilofar Danishmalik Sayyed, Yeon-Ju Lee, Hye-Yoon Jeon, Eun-Bin Kim, Seok-Ho Hong, Soyeon Cho, Minsoo Kim, Kwon-Soo Ha. Midazolam Ameliorates Hyperglycemia-Induced Glomerular Endothelial Dysfunction by Inhibiting Transglutaminase 2 in Diabetes.
International journal of molecular sciences.
2022 Jan; 23(2):. doi:
10.3390/ijms23020753
. [PMID: 35054938] - Dirk Kropeit, David McCormick, Katharina Erb-Zohar, Hans-Peter Stobernack, Holger Zimmermann, Helga Rübsamen-Schaeff. Pharmacokinetics and Safety of Letermovir and Midazolam Coadministration in Healthy Subjects.
Clinical pharmacology in drug development.
2022 01; 11(1):16-24. doi:
10.1002/cpdd.1027
. [PMID: 34714967] - Yuanyuan Gao, Fei Yan. Comparison of Intra and Post-operative Sedation Efficacy of Dexmedetomidinemidazolam and Dexmedetomidine-propofol for Major Abdominal Surgery.
Current drug metabolism.
2022; 23(1):45-56. doi:
10.2174/1389200222666211103121832
. [PMID: 34732114] - Camille Lenoir, Amine Niederer, Victoria Rollason, Jules Alexandre Desmeules, Youssef Daali, Caroline Flora Samer. Prediction of cytochromes P450 3A and 2C19 modulation by both inflammation and drug interactions using physiologically based pharmacokinetics.
CPT: pharmacometrics & systems pharmacology.
2022 01; 11(1):30-43. doi:
10.1002/psp4.12730
. [PMID: 34791831] - Issei Fujita, Hiroshi Watanabe, Komei Ikegami, Tadashi Imafuku, Shota Ichimizu, Mayuko Chikamatsu, Kazuki Kobayashi, Ryusei Tanaka, Koichi Yamada, Hitoshi Maeda, Toru Maruyama. Involvement of the Parathyroid Hormone-Related Protein on Changes in the CYP3A Expression in Cancer Cachexia.
Molecular pharmaceutics.
2021 12; 18(12):4322-4330. doi:
10.1021/acs.molpharmaceut.1c00490
. [PMID: 34734526] - Fabio Bachmann, Urs Duthaler, Stephan Krähenbühl. Effect of deglucuronidation on the results of the Basel phenotyping cocktail.
British journal of clinical pharmacology.
2021 12; 87(12):4608-4618. doi:
10.1111/bcp.14874
. [PMID: 33890704] - Sarah Nakhodchi, Naader Alizadeh. Rapid simultaneous determination of ketamine and midazolam in biological samples using ion mobility spectrometry combined by headspace solid-phase microextraction.
Journal of chromatography. A.
2021 Nov; 1658(?):462609. doi:
10.1016/j.chroma.2021.462609
. [PMID: 34656845] - Hope Douglas, Klaus Hopster, Michelle Cerullo, Charlotte Hopster-Iversen, Darko Stefanovski, Bernd Driessen. The effects of flumazenil on ventilatory and recovery characteristics in horses following midazolam-ketamine induction and isoflurane anaesthesia.
Equine veterinary journal.
2021 Nov; 53(6):1257-1267. doi:
10.1111/evj.13391
. [PMID: 33220066] - Marius Bogdan Novac, Lidia Boldeanu, Luciana Teodora Rotaru, Anda Lorena Dijmărescu, Mircea Sebastian Şerbănescu, Lucreţiu Radu, Simona Daniela Neamţu, Alina Maria Vîlcea, Mihaela Niculescu, Cecil Sorin Mirea, Mihail Virgil Boldeanu, Maria Magdalena Manolea. The perioperative effect of anesthetic drugs on the immune response in total intravenous anesthesia in patients undergoing minimally invasive gynecological surgery.
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie.
2021 Oct; 62(4):961-969. doi:
10.47162/rjme.62.4.08
. [PMID: 35673815] - Ling Yao, Bo Liu, Tianhui He, Feng Shen. [Comparative study of dexmedetomidine vs. midazolam on plasma catecholamine levels and hemodynamics in patients with septic shock].
Zhonghua wei zhong bing ji jiu yi xue.
2021 Oct; 33(10):1193-1197. doi:
10.3760/cma.j.cn121430-20210119-00105
. [PMID: 34955127] - Meliha Aksoy Okan, Derya Büyükkayhan, Güner Karatekin. The Effect of Midazolam on Oxidative Stress and Apoptosis in Preterm Infants.
Fetal and pediatric pathology.
2021 Oct; 40(5):423-429. doi:
10.1080/15513815.2020.1721627
. [PMID: 32000555] - Sara N Salerno, Fernando O Carreño, Andrea N Edginton, Michael Cohen-Wolkowiez, Daniel Gonzalez. Leveraging Physiologically Based Pharmacokinetic Modeling and Experimental Data to Guide Dosing Modification of CYP3A-Mediated Drug-Drug Interactions in the Pediatric Population.
Drug metabolism and disposition: the biological fate of chemicals.
2021 09; 49(9):844-855. doi:
10.1124/dmd.120.000318
. [PMID: 34154994] - Kaoru Toyama, Hidetoshi Furuie, Kana Kuroda, Tomoko Ishizuka, Yasuyuki Okuda, Takako Shimizu, Manabu Kato, Yoshiyuki Igawa, Yasuhiro Nishikawa, Hitoshi Ishizuka. Effects of Repeated Oral Administration of Esaxerenone on the Pharmacokinetics of Midazolam in Healthy Japanese Males.
European journal of drug metabolism and pharmacokinetics.
2021 Sep; 46(5):685-694. doi:
10.1007/s13318-021-00701-4
. [PMID: 34383278] - Xiaoshu Dai, Michael D Karol, Matthew Hitron, Marjie L Hard, Matthew T Goulet, Colleen F McLaughlin, Scott J Brantley. Napabucasin Drug-Drug Interaction Potential, Safety, Tolerability, and Pharmacokinetics Following Oral Dosing in Healthy Adult Volunteers.
Clinical pharmacology in drug development.
2021 08; 10(8):824-839. doi:
10.1002/cpdd.961
. [PMID: 34107166] - Valeria Ottaviano, Alessandro Mauro Tavone, Claudia Scipione, Saverio Potenza, Giulia Petroni, Gian Luca Marella. Drug detection in decomposed cadavers confirms testimonial evidence in a case of serial homicides.
Forensic science international.
2021 Aug; 325(?):110893. doi:
10.1016/j.forsciint.2021.110893
. [PMID: 34273605] - Harumi Yoshinaga, Arturo Benitez, Shinichi Takeda, Martha Fournier, Alan R Kugler. A Phase 3 open-label study of the efficacy, safety and pharmacokinetics of buccally administered midazolam hydrochloride for the treatment of status epilepticus in pediatric Japanese subjects.
Epilepsy research.
2021 08; 174(?):106651. doi:
10.1016/j.eplepsyres.2021.106651
. [PMID: 34020149] - A David Rodrigues, Madelé van Dyk, Michael J Sorich, Alia Fahmy, Zivile Useckaite, Lauren A Newman, Asha J Kapetas, Reham Mounzer, Linda S Wood, Jillian G Johnson, Andrew Rowland. Exploring the Use of Serum-Derived Small Extracellular Vesicles as Liquid Biopsy to Study the Induction of Hepatic Cytochromes P450 and Organic Anion Transporting Polypeptides.
Clinical pharmacology and therapeutics.
2021 07; 110(1):248-258. doi:
10.1002/cpt.2244
. [PMID: 33792897] - Jayaprakasam Bolleddula, Alice Ke, Hua Yang, Chandra Prakash. PBPK modeling to predict drug-drug interactions of ivosidenib as a perpetrator in cancer patients and qualification of the Simcyp platform for CYP3A4 induction.
CPT: pharmacometrics & systems pharmacology.
2021 06; 10(6):577-588. doi:
10.1002/psp4.12619
. [PMID: 33822485] - Carmen Flores-Pérez, Manuel de Jesús Castillejos-López, Juan Luis Chávez-Pacheco, Víctor Manuel Dávila-Borja, Janett Flores-Pérez, Patricia Zárate-Castañón, Mario Acosta-Bastidas, Jonathan Cruz-Escobar, Luz María Torres-Espíndola. The rs776746 variant of CYP3A5 is associated with intravenous midazolam plasma levels and higher clearance in critically ill Mexican paediatric patients.
Journal of clinical pharmacy and therapeutics.
2021 Jun; 46(3):633-639. doi:
10.1111/jcpt.13388
. [PMID: 33638195] - Wushuang Zeng, Lanlan Gui, Xianwen Tan, Pingping Zhu, Yiting Hu, Qingliang Wu, Xuejing Li, Lian Yang, Wei Jia, Changxiao Liu, Ke Lan. Tertiary Oxidation of Deoxycholate Is Predictive of CYP3A Activity in Dogs.
Drug metabolism and disposition: the biological fate of chemicals.
2021 05; 49(5):369-378. doi:
10.1124/dmd.121.000385
. [PMID: 33674269] - Iwona Zaporowska-Stachowiak, Tomasz Grabowski, Katarzyna Stachowiak-Szymczak, Karolina Gościniak, Artur Teżyk, Maciej Sopata. Midazolam and hydroxymidazolam plasma concentrations can be monitored with selected biochemical and physiological parameters of palliative care patients.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.
2021 May; 137(?):111304. doi:
10.1016/j.biopha.2021.111304
. [PMID: 33550045] - James T Nguyen, Dan-Dan Tian, Rakshit S Tanna, Deena L Hadi, Sumit Bansal, Justina C Calamia, Christopher M Arian, Laura M Shireman, Bálint Molnár, Miklós Horváth, Joshua J Kellogg, Matthew E Layton, John R White, Nadja B Cech, Richard D Boyce, Jashvant D Unadkat, Kenneth E Thummel, Mary F Paine. Assessing Transporter-Mediated Natural Product-Drug Interactions Via In vitro-In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail.
Clinical pharmacology and therapeutics.
2021 05; 109(5):1342-1352. doi:
10.1002/cpt.2107
. [PMID: 33174626] - Frédérik Rousseau-Blass, Alastair E Cribb, Francis Beaudry, Daniel Sj Pang. A Pharmacokinetic-Pharmacodynamic Study of Intravenous Midazolam and Flumazenil in Adult New Zealand White-Californian Rabbits (Oryctolagus cuniculus).
Journal of the American Association for Laboratory Animal Science : JAALAS.
2021 05; 60(3):319-328. doi:
10.30802/aalas-jaalas-20-000084
. [PMID: 33673881] - Jana Grass, Peter Rose, Jürgen Burhenne, Antje Blank, Walter Emil Haefeli, Gerd Mikus. Absolute Bioavailability of Microdosed Midazolam After Buccal Administration Is Dependent on Buccal Exposure Time.
Journal of clinical pharmacology.
2021 04; 61(4):472-479. doi:
10.1002/jcph.1751
. [PMID: 32976642] - Abraham J Valkenburg, Sebastiaan C Goulooze, Cormac V Breatnach, Ron A A Mathôt, Dick Tibboel, Monique van Dijk, Catherijne A J Knibbe, Mariska Y M Peeters. Sedation With Midazolam After Cardiac Surgery in Children With and Without Down Syndrome: A Pharmacokinetic-Pharmacodynamic Study.
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
2021 04; 22(4):e259-e269. doi:
10.1097/pcc.0000000000002580
. [PMID: 33031353] - M René Bouw, Steve S Chung, Barry Gidal, Aliceson King, Jerry Tomasovic, James W Wheless, Peter J Van Ess. Clinical pharmacokinetic and pharmacodynamic profile of midazolam nasal spray.
Epilepsy research.
2021 03; 171(?):106567. doi:
10.1016/j.eplepsyres.2021.106567
. [PMID: 33607532] - Irene Scholz, Evangelia Liakoni, Felix Hammann, Katharina Elisabeth Grafinger, Urs Duthaler, Michael Nagler, Stephan Krähenbühl, Manuel Haschke. Effects of Hypericum perforatum (St John's wort) on the pharmacokinetics and pharmacodynamics of rivaroxaban in humans.
British journal of clinical pharmacology.
2021 03; 87(3):1466-1474. doi:
10.1111/bcp.14553
. [PMID: 32959922] - Abhishek G Sathe, Ahmed A Othman, Mohamed-Eslam F Mohamed. Therapeutic Protein Drug Interaction Potential in Subjects With Psoriasis: An Assessment Based on Population Pharmacokinetic Analyses of Sensitive Cytochrome P450 Probe Substrates.
Journal of clinical pharmacology.
2021 03; 61(3):307-318. doi:
10.1002/jcph.1744
. [PMID: 32960975] - Sara Batista do Nascimento, Mariana de Lima Nascimento, Joaquim Maurício Duarte-Almeida, Flávio Martins de Oliveira, Maria do Carmo Vieira, João Máximo Siqueira, Frank Pereira de Andrade, Isabela da Costa César, Whocely Victor de Castro. Validation of a HPLC method for quantification of midazolam in rat plasma: Application during a Maytenus ilicifolia-drug interaction study.
Biomedical chromatography : BMC.
2021 Mar; 35(3):e4999. doi:
10.1002/bmc.4999
. [PMID: 33460183] - Ingrid Anna Teigen, Jon Andsnes Berg, Kristoffer Brodwall. An apathetic child with hallucinations.
Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke.
2021 02; 141(3):. doi:
10.4045/tidsskr.20.0569
. [PMID: 33624976] - Xin Wang, Ping Xiang, Olaf H Drummer, Jiaojiao Ji, Yue Zhuo, Gengli Duan, Min Shen. Pharmacokinetic study of midazolam and α-hydroxymidazolam in guinea pig blood and hair roots after a single dose of midazolam.
Journal of pharmaceutical and biomedical analysis.
2021 Feb; 195(?):113890. doi:
10.1016/j.jpba.2021.113890
. [PMID: 33454503] - Brenda M Marrero-Rosado, Michael F Stone, Marcio de Araujo Furtado, Caroline R Schultz, C Linn Cadieux, Lucille A Lumley. Novel Genetically Modified Mouse Model to Assess Soman-Induced Toxicity and Medical Countermeasure Efficacy: Human Acetylcholinesterase Knock-in Serum Carboxylesterase Knockout Mice.
International journal of molecular sciences.
2021 Feb; 22(4):. doi:
10.3390/ijms22041893
. [PMID: 33672922] - Soyoung Lee, Yujin Lee, Andrew HyoungJin Kim, Sumin Yoon, Jieon Lee, Sang Chun Ji, Seo Hyun Yoon, SeungHwan Lee, Kyung-Sang Yu, In-Jin Jang, Joo-Youn Cho. Urinary metabolic markers reflect on hepatic, not intestinal, CYP3A activity in healthy subjects.
Drug metabolism and pharmacokinetics.
2021 Feb; 36(?):100374. doi:
10.1016/j.dmpk.2020.12.001
. [PMID: 33348239] - Daniel A Tatosian, Ka Lai Yee, Zufei Zhang, Kate Mostoller, Erina Paul, Santosh Sutradhar, Patrick Larson, Aparna Chhibber, Jianzhong Wen, Ya-Juan Wang, Michael Lassman, Andrew H Latham, Jianmei Pang, Tami Crumley, Anne Gillespie, Nadia Cardillo Marricco, Ted Marenco, Matthew Murphy, Kenneth C Lasseter, Thomas C Marbury, Donald Tweedie, Xiaoyan Chu, Raymond Evers, S Aubrey Stoch. A Microdose Cocktail to Evaluate Drug Interactions in Patients with Renal Impairment.
Clinical pharmacology and therapeutics.
2021 02; 109(2):403-415. doi:
10.1002/cpt.1998
. [PMID: 32705692] - Xiaozu Liao, Zhou Cheng, Junlin Wen, Binfei Li. A Case Report of Sedation Strategy for a Patient With Coronavirus Disease 2019 Supported by Extracorporeal Membrane Oxygenation After Cesarean Section.
The heart surgery forum.
2021 01; 24(1):E019-E021. doi:
10.1532/hsf.3459
. [PMID: 33635242] - Youyi Peng, Qiang Zhang, William J Welsh. Novel Sigma 1 Receptor Antagonists as Potential Therapeutics for Pain Management.
Journal of medicinal chemistry.
2021 01; 64(1):890-904. doi:
10.1021/acs.jmedchem.0c01964
. [PMID: 33372782] - Shaopeng Ming, Yongguo Xie, Xueke Du, Haiqing Huang, Yue Fan, Qingxuan Liang, Yubo Xie. Effect of dexmedetomidine on perioperative hemodynamics and organ protection in children with congenital heart disease: A randomized controlled trial.
Medicine.
2021 Jan; 100(1):e23998. doi:
10.1097/md.0000000000023998
. [PMID: 33429762] - Kun Hu, Qian Xiang, Zhe Wang, Xiaoyan Sheng, Li'e Li, Yan Liang, Xia Zhao, Xia Ye, Yimin Cui. Effects of Vitamin D Receptor, Cytochrome P450 3A, and Cytochrome P450 Oxidoreductase Genetic Polymorphisms on the Pharmacokinetics of Remimazolam in Healthy Chinese Volunteers.
Clinical pharmacology in drug development.
2021 01; 10(1):22-29. doi:
10.1002/cpdd.797
. [PMID: 32250057] - A Mireille A Wessels, Mathieu S Bolhuis, Wouter Bult, Maarten W N Nijsten, Martin C J Kneyber, Daan J Touw. A fast and simple method for the simultaneous analysis of midazolam, 1-hydroxymidazolam, 4-hydroxymidazolam and 1-hydroxymidazolam glucuronide in human serum, plasma and urine.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.
2021 Jan; 1162(?):122476. doi:
10.1016/j.jchromb.2020.122476
. [PMID: 33385770] - Xingyi Zhao, Minpeng Ji, Xin Wen, Dan Chen, Fu Huang, Xiaoju Guan, Jing Tian, Jiajia Xie, Jingjing Shao, Jiexia Wang, Luoqi Huang, Han Lin, Leping Ye, Haolin Chen. Effects of Midazolam on the Development of Adult Leydig Cells From Stem Cells In Vitro.
Frontiers in endocrinology.
2021; 12(?):765251. doi:
10.3389/fendo.2021.765251
. [PMID: 34867807] - Motoyasu Miura, Shimako Tanaka, Shinya Uchida, Chiaki Kamiya, Naoki Katayama, Akio Hakamata, Keiichi Odagiri, Naoki Inui, Junichi Kawakami, Hiroshi Watanabe, Noriyuki Namiki. Prediction of the Area under the Curve Using Limited-Point Blood Sampling in a Cocktail Study to Assess Multiple CYP Activities.
Biological & pharmaceutical bulletin.
2021; 44(6):762-770. doi:
10.1248/bpb.b20-00691
. [PMID: 34078808] - Luca Zombori, Melody Bacon, Hannah Wood, Fiona Chatterjee, Ramesh Venkateswaran, Simona Lampariello, Michael Yoong. Severe cortical damage associated with COVID-19 case report.
Seizure.
2021 Jan; 84(?):66-68. doi:
10.1016/j.seizure.2020.11.014
. [PMID: 33285362] - Erica R Kundrick, Brenda M Marrero-Rosado, Marcio de Araujo Furtado, Michael Stone, Caroline R Schultz, Lucille A Lumley. Cannabidiol reduces soman-induced lethality and seizure severity in female plasma carboxylesterase knockout mice treated with midazolam.
Neurotoxicology.
2021 01; 82(?):130-136. doi:
10.1016/j.neuro.2020.12.002
. [PMID: 33290784] - Rakshit S Tanna, Dan-Dan Tian, Nadja B Cech, Nicholas H Oberlies, Allan E Rettie, Kenneth E Thummel, Mary F Paine. Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations.
The Journal of pharmacology and experimental therapeutics.
2021 01; 376(1):64-73. doi:
10.1124/jpet.120.000270
. [PMID: 33093187] - Taavi J K Kaartinen, Aleksi Tornio, Tuija Tapaninen, Terhi Launiainen, Nina Isoherranen, Mikko Niemi, Janne T Backman. Effect of High-Dose Esomeprazole on CYP1A2, CYP2C19, and CYP3A4 Activities in Humans: Evidence for Substantial and Long-lasting Inhibition of CYP2C19.
Clinical pharmacology and therapeutics.
2020 12; 108(6):1254-1264. doi:
10.1002/cpt.1949
. [PMID: 32558923] - Takayuki Katsube, Yuji Inoue, Takahiro Fukuhara, Takeshi Kano, Toshihiro Wajima. Evaluation of drug-drug interaction of lusutrombopag, a thrombopoietin receptor agonist, via metabolic enzymes and transporters.
European journal of clinical pharmacology.
2020 Dec; 76(12):1659-1665. doi:
10.1007/s00228-020-02960-7
. [PMID: 32666123] - Bianca D van Groen, Esther van Duijn, Arjan de Vries, Miriam G Mooij, Dick Tibboel, Wouter H J Vaes, Saskia N de Wildt. Proof of Concept: First Pediatric [14 C]microtracer Study to Create Metabolite Profiles of Midazolam.
Clinical pharmacology and therapeutics.
2020 11; 108(5):1003-1009. doi:
10.1002/cpt.1884
. [PMID: 32386327] - Yaowei Zhu, Yan Xu, Yanli Zhuang, Alexa Piantone, Cathye Shu, Dion Chen, Honghui Zhou, Zhenhua Xu, Amarnath Sharma. Evaluating Potential Disease-Mediated Protein-Drug Interactions in Patients With Moderate-to-Severe Plaque Psoriasis Receiving Subcutaneous Guselkumab.
Clinical and translational science.
2020 11; 13(6):1217-1226. doi:
10.1111/cts.12807
. [PMID: 32407591] - Roberta Natália Cestari, Renê Donizeti Ribeiro de Oliveira, Flávio Falcão Lima de Souza, Leandro Francisco Pippa, Glauco Henrique Balthazar Nardotto, Adriana Rocha, Eduardo Antônio Donadi, Vera Lucia Lanchote. Systemic Lupus Erythematosus Activity Affects the Sinusoidal Uptake Transporter OATP1B1 Evaluated by the Pharmacokinetics of Atorvastatin.
Clinical and translational science.
2020 11; 13(6):1227-1235. doi:
10.1111/cts.12808
. [PMID: 32463566] - Erica Kundrick, Brenda Marrero-Rosado, Michael Stone, Caroline Schultz, Katie Walker, Robyn B Lee-Stubbs, Marcio de Araujo Furtado, Lucille A Lumley. Delayed midazolam dose effects against soman in male and female plasma carboxylesterase knockout mice.
Annals of the New York Academy of Sciences.
2020 11; 1479(1):94-107. doi:
10.1111/nyas.14311
. [PMID: 32027397] - Yibo Zhang, Chao Li, Jingjing Shi, Yanming Gong, Tao Zeng, Min Lin, Xi Zhang. Comparison of dexmedetomidine with midazolam for dental surgery: A systematic review and meta-analysis.
Medicine.
2020 Oct; 99(43):e22288. doi:
10.1097/md.0000000000022288
. [PMID: 33120732] - Kuan-Fu Chen, Lingtak-Neander Chan, Yvonne S Lin. PBPK modeling of CYP3A and P-gp substrates to predict drug-drug interactions in patients undergoing Roux-en-Y gastric bypass surgery.
Journal of pharmacokinetics and pharmacodynamics.
2020 10; 47(5):493-512. doi:
10.1007/s10928-020-09701-4
. [PMID: 32710209] - Conall Francoeur, Sarah S Welsh, Rebecca Ichord, Nicholas S Abend, Alexis A Topjian, Athena F Zuppa. Assessment of midazolam pharmacokinetics in the treatment of status epilepticus.
Seizure.
2020 Oct; 81(?):310-314. doi:
10.1016/j.seizure.2020.09.004
. [PMID: 32947180] - Carol Loretz, Ming-Chih David Ho, Novera Alam, Walter Mitchell, Albert P Li. Application of Cryopreserved Human Intestinal Mucosa and Cryopreserved Human Enterocytes in the Evaluation of Herb-Drug Interactions: Evaluation of CYP3A Inhibitory Potential of Grapefruit Juice and Commercial Formulations of Twenty-Nine Herbal Supplements.
Drug metabolism and disposition: the biological fate of chemicals.
2020 10; 48(10):1084-1091. doi:
10.1124/dmd.120.000033
. [PMID: 32719085] - Timothy Jackson, Katie Hobson, Hannah Clare, Daniel Weegmann, Catherine Moloughney, Sally McManus. End-of-life care in COVID-19: An audit of pharmacological management in hospital inpatients.
Palliative medicine.
2020 10; 34(9):1235-1240. doi:
10.1177/0269216320935361
. [PMID: 32588748] - Erlend Johannessen Egeland, Bartlomiej J Witczak, Hasse Khiabani Zaré, Hege Christensen, Anders Åsberg, Ida Robertsen. Chronic Inhibition of CYP3A is Temporarily Reduced by Each Hemodialysis Session in Patients With End-Stage Renal Disease.
Clinical pharmacology and therapeutics.
2020 10; 108(4):866-873. doi:
10.1002/cpt.1875
. [PMID: 32356565] - Jan de Jong, Anna Mitselos, Wojciech Jurczak, Raul Cordoba, Carlos Panizo, Tomasz Wrobel, Monika Dlugosz-Danecka, James Jiao, Juthamas Sukbuntherng, Daniele Ouellet, Peter Hellemans. Ibrutinib does not have clinically relevant interactions with oral contraceptives or substrates of CYP3A and CYP2B6.
Pharmacology research & perspectives.
2020 10; 8(5):e00649. doi:
10.1002/prp2.649
. [PMID: 32945596] - Brenda M Marrero-Rosado, Marcio de Araujo Furtado, Erica R Kundrick, Katie A Walker, Michael F Stone, Caroline R Schultz, Donna A Nguyen, Lucille A Lumley. Ketamine as adjunct to midazolam treatment following soman-induced status epilepticus reduces seizure severity, epileptogenesis, and brain pathology in plasma carboxylesterase knockout mice.
Epilepsy & behavior : E&B.
2020 10; 111(?):107229. doi:
10.1016/j.yebeh.2020.107229
. [PMID: 32575012] - Frank Schippers, Marija Pesic, Robert Saunders, Keith Borkett, Shawn Searle, Lynn Webster, Thomas Stoehr. Randomized Crossover Trial to Compare Abuse Liability of Intravenous Remimazolam Versus Intravenous Midazolam and Placebo in Recreational Central Nervous System Depressant Users.
Journal of clinical pharmacology.
2020 09; 60(9):1189-1197. doi:
10.1002/jcph.1614
. [PMID: 32495449] - Tanay S Samant, Felix Huth, Kenichi Umehara, Hilmar Schiller, Shyeilla V Dhuria, Mohamed Elmeliegy, Michelle Miller, Abhijit Chakraborty, Tycho Heimbach, Handan He, Yan Ji. Ribociclib Drug-Drug Interactions: Clinical Evaluations and Physiologically-Based Pharmacokinetic Modeling to Guide Drug Labeling.
Clinical pharmacology and therapeutics.
2020 09; 108(3):575-585. doi:
10.1002/cpt.1950
. [PMID: 32557601] - P Kellie Turner, Stephen D Hall, Sonya C Chapman, Jessica L Rehmel, Jane E Royalty, Yingying Guo, Palaniappan Kulanthaivel. Abemaciclib Does Not Have a Clinically Meaningful Effect on Pharmacokinetics of CYP1A2, CYP2C9, CYP2D6, and CYP3A4 Substrates in Patients with Cancer.
Drug metabolism and disposition: the biological fate of chemicals.
2020 09; 48(9):796-803. doi:
10.1124/dmd.119.090092
. [PMID: 32581049] - Weiyi Gong, Shuguang Zhang, Xiaoliang Li, Lei Shi. Dexmedetomidine is superior to midazolam for sedation and cerebral protection in postoperative hypertensive intracerebral hemorrhage patients: a retrospective study.
The Journal of international medical research.
2020 Sep; 48(9):300060520957554. doi:
10.1177/0300060520957554
. [PMID: 32967514] - Xia Li, Lisa Junge, Max Taubert, Anabelle von Georg, Dominik Dahlinger, Chris Starke, Sebastian Frechen, Christoph Stelzer, Martina Kinzig, Fritz Sörgel, Ulrich Jaehde, Ulrich Töx, Tobias Goeser, Uwe Fuhr. A Novel Study Design Using Continuous Intravenous and Intraduodenal Infusions of Midazolam and Voriconazole for Mechanistic Quantitative Assessment of Hepatic and Intestinal CYP3A Inhibition.
Journal of clinical pharmacology.
2020 09; 60(9):1237-1253. doi:
10.1002/jcph.1619
. [PMID: 32427354] - Yelizaveta Sher, Beatrice Rabkin, José R Maldonado, Paul Mohabir. COVID-19-Associated Hyperactive Intensive Care Unit Delirium With Proposed Pathophysiology and Treatment: A Case Report.
Psychosomatics.
2020 Sep; 61(5):544-550. doi:
10.1016/j.psym.2020.05.007
. [PMID: 32591212] - Joonho Jeong, Kyoungwon Jung, Kwang Il Seo, Byung Cheol Yun, Byung Hoon Han, Sang Uk Lee, Won Moon. Propofol alone prevents worsening hepatic encephalopathy rather than midazolam alone or combined sedation after esophagogastroduodenoscopy in compensated or decompensated cirrhotic patients.
European journal of gastroenterology & hepatology.
2020 08; 32(8):1054-1061. doi:
10.1097/meg.0000000000001755
. [PMID: 32433420] - Ken Ogasawara, Patricia M LoRusso, Anthony J Olszanski, Olivier Rixe, Christine Xu, Jian Yin, Maria Palmisano, Gopal Krishna. Assessment of effects of repeated oral doses of fedratinib on inhibition of cytochrome P450 activities in patients with solid tumors using a cocktail approach.
Cancer chemotherapy and pharmacology.
2020 07; 86(1):87-95. doi:
10.1007/s00280-020-04102-3
. [PMID: 32537715] - Benjamin Berger, Priska Kaufmann, Annelize Koch, Jasper Dingemanse. Impact of the Selective Orexin-1 Receptor Antagonist ACT-539313 on the Pharmacokinetics of the CYP3A Probe Drug Midazolam in Healthy Male Subjects.
Journal of clinical pharmacology.
2020 07; 60(7):931-941. doi:
10.1002/jcph.1588
. [PMID: 32035014] - J Jedamzik, J Mühlbacher, F Fitschek, C Schwarz, J Burhenne, U Asenbaum, K Kaczirek, G Mikus. No alteration of Cyp3A4 activity after major hepatectomy in the early postoperative period - A prospective before-after study.
International journal of surgery (London, England).
2020 Jul; 79(?):131-135. doi:
10.1016/j.ijsu.2020.05.010
. [PMID: 32413504] - Younah Kim, Jung Jae Jo, Piljoung Cho, Riya Shrestha, Kyu Min Kim, Sung Hwan Ki, Kyung-Sik Song, Kwang-Hyeon Liu, Im-Sook Song, Ju-Hyun Kim, Jae-Mok Lee, Sangkyu Lee. Characterization of red ginseng-drug interaction by CYP3A activity increased in high dose administration in mice.
Biopharmaceutics & drug disposition.
2020 Jul; 41(7):295-306. doi:
10.1002/bdd.2246
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