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https://www.readbyqxmd.com/read/29136681/assessment-of-multiple-cytochrome-p450-activities-in-metabolically-inactivated-human-liver-microsomes-and-roles-of-p450-2c-isoforms-in-reaction-phenotyping-studies
#1
Norie Murayama, Kanako Yajima, Mikiko Hikawa, Kanami Shimura, Yu Ishii, Masaki Takada, Yasuhiro Uno, Masahiro Utoh, Kazuhide Iwasaki, Hiroshi Yamazaki
The fraction of substrate metabolized (fm ) can be used to estimate drug interactions and can be determined by comparison of the intrinsic clearances (CLint ) of victim drugs obtained from inhibited and uninhibited hepatic enzymes. Commercially available human liver microsomes were recently developed in which one cytochrome P450 (P450) isoform is selectively inactivated. These inactivated liver microsomes were used to evaluate the roles of P450 2C isoforms in the depletion and oxidation of probe substrates...
November 14, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29128692/coast-cisplatin-ototoxicity-attenuated-by-aspirin-trial-a-phase-ii-double-blind-randomised-controlled-trial-to-establish-if-aspirin-reduces-cisplatin-induced-hearing-loss
#2
Simon J Crabb, Karen Martin, Julia Abab, Ian Ratcliffe, Roger Thornton, Ben Lineton, Mary Ellis, Ronald Moody, Louise Stanton, Angeliki Galanopoulou, Tom Maishman, Thomas Geldart, Mike Bayne, Joe Davies, Carolynn Lamb, Sanjay Popat, Johnathan K Joffe, Chris Nutting, John Chester, Andrew Hartley, Gareth Thomas, Christian Ottensmeier, Robert Huddart, Emma King
BACKGROUND: Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy. METHODS: A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle...
November 9, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29119032/cytomegalovirus-associated-duodenal-ulcer-and-duodenitis-in-a-malnourished-pediatric-patient
#3
Rachel Bernard, Ghanim Aljomah, Emily Klepper, Elizabeth McDonough
Cytomegalovirus (CMV) duodenitis is a rare occurrence, especially in pediatric patients. A thirteen-month-old female presented to the Emergency Department for a febrile seizure. She was incidentally admitted for severe malnutrition with an initial workup remarkable for only a slight elevation in her ALT at 48. The patient was found to have an oral aversion requiring nasogastric tube feeds for adequate caloric intake. She continued to fail to gain weight and underwent an EGD that demonstrated a duodenal ulcer...
2017: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/29115998/effect-of-gastric-acid-suppressive-therapy-and-biological-variation-of-serum-gastrin-concentrations-in-dogs-with-chronic-enteropathies
#4
Romy M Heilmann, Nora Berghoff, Niels Grützner, Nolie K Parnell, Jan S Suchodolski, Jörg M Steiner
BACKGROUND: Serum gastrin concentration can help diagnose gastrinomas in dogs if >3-10× the upper reference limit (URL), but antisecretory therapy and other conditions can also cause hypergastrinemia. Effects of antisecretory therapy (famotidine or ranitidine, omeprazole) on serum gastrin concentration in dogs with chronic enteropathy (CE) and its biological variation (BV) are unknown. Aim of the study was to evaluate serum gastrin in acid-suppressant-treated or -naïve CE dogs; test the association between serum gastrin and histopathologic findings in acid-suppressant-naïve CE dogs; and evaluate the BV of serum gastrin in dogs not receiving any gastric acid suppressive therapy...
November 7, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29115994/exploring-venlafaxine-pharmacokinetic-variability-with-a-phenotyping-approach-a-multicentric-french-swiss-study-marvel-study
#5
Célia Lloret-Linares, Youssef Daali, Sylvie Chevret, Isabelle Nieto, Fanny Molière, Philippe Courtet, Florence Galtier, Raphaëlle-Marie Richieri, Sophie Morange, Pierre-Michel Llorca, Wissam El-Hage, Thomas Desmidt, Frédéric Haesebaert, Philippe Vignaud, Jerôme Holtzmann, Jean-Luc Cracowski, Marion Leboyer, Antoine Yrondi, Fabienne Calvas, Liova Yon, Philippe Le Corvoisier, Olivier Doumy, Kyle Heron, Damien Montange, Siamak Davani, Julien Déglon, Marie Besson, Jules Desmeules, Emmanuel Haffen, Frank Bellivier
BACKGROUND: It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the "in vivo" measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis...
November 7, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29105855/dicloxacillin-induces-cyp2c19-cyp2c9-and-cyp3a4-in-vivo-and-in-vitro
#6
Tore Bjerregaard Stage, Magnus Graff, Susan Wong, Louise Ladebo Rasmussen, Flemming Nielsen, Anton Pottegård, Kim Brøsen, Deanna L Kroetz, S Cyrus Khojasteh, Per Damkier
AIM: The aim of this study was to study potential cytochrome P450 induction by dicloxacillin. METHODS: We performed an open-label randomized two-phase 5-drug clinical pharmacokinetic cocktail crossover study in 12 healthy men with and without pretreatment with 1g dicloxacillin three times daily for 10 days. Plasma and urine was collected over 24 hours and the concentration of all five drugs and their primary metabolites was determined using a LC-MS/MS method. Cryopreserved primary human hepatocytes were exposed to dicloxacillin for 48h and changes in gene expression and enzyme activity of CYP3A4, CYP2C9, CYP2B6 and CYP1A2 was investigated...
November 4, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29100966/the-detection-and-quantification-in-vivo-and-in-real-time-of-hydrogen-sulfide-in-ethanol-induced-lesions-in-rat-stomachs-using-an-ion-sensitive-electrode
#7
Josué A Velázquez-Moyado, Andrés Navarrete
INTRODUCTION: The development of electrochemical sensors for the detection of small molecules has already had a significant effect on the study of biology because of their selectivity and ability to measure low concentrations of small molecules that regulate various functions in living organisms. Hydrogen sulfide (H2S) is a gasotransmitter produced at low levels in several tissues including the stomach. Here, we propose a new method for detecting low concentrations of this transmitter in the rat stomach, in-vivo and in real time, with applications in pharmacology and physiology...
October 31, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29099060/clinical-pharmacogenetics-of-cytochrome-p450-associated-drugs-in-children
#8
Ida Aka, Christiana J Bernal, Robert Carroll, Angela Maxwell-Horn, Kazeem A Oshikoya, Sara L Van Driest
Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In order to understand the frequency of pediatric exposures to drugs with known CYP interactions, we compiled all actionable drug-CYP interactions with a high level of evidence using Clinical Pharmacogenomic Implementation Consortium (CPIC) data and surveyed 10 years of electronic health records (EHR) data for the number of children exposed to CYP-associated drugs...
November 2, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29065836/stability-indicating-liquid-chromatographic-method-for-simultaneous-determination-of-aspirin-and-omeprazole
#9
Vandana B Patel, Aishwarya D Patel, Dimal A Shah
BACKGROUND: Aspirin combination is prescribed for the its thrombolytic activity where gastric ulceration is the major side effects of aspirin which can be prevented by combining it with proton pump inhibitor omeprazole. Present study describes development of analytical method for the estimation of aspirin and omeprazole in combination. Objective of the present study was to develop and validate chromatographic method for simultaneous analysis of aspirin and omeprazole. METHODS: Isocratic, reversed phase stability indicating liquid chromatographic method was developed for the simultaneous determination of Aspirin and Omeprazole in combination...
October 23, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/29063606/harnessing-meta-analysis-to-refine-an-oncology-patient-population-for-physiology-based-pharmacokinetic-modeling-of-drugs
#10
Emily Schwenger, Venkatesh Pilla Reddy, Ganesh Moorthy, Pradeep Sharma, Helen Tomkinson, Eric Masson, Karthick Vishwanathan
Certain oncology compounds exhibit fundamental PK disparities between healthy and malignant conditions. Given the effects of tumor-associated inflammation on enzyme and transporter expression, we performed a meta-analysis of CYP- and transporter-sensitive substrate clinical PK to quantitatively compare enzyme and transporter abundances between healthy volunteers (HV) and cancer patients (CP). Hepatic and intestinal CYP1A2, CYP2C19, and CYP3A4 abundance were subsequently adjusted via Simcyp®'s sensitivity analysis tool...
October 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29060457/a-pharmacokinetic-model-of-drug-drug-interaction-between-clopidogrel-and-omeprazole-at-cyp2c19-in-humans
#11
Wimonchat Tangamornsuksan, Pongpak Thiansupornpong, Thirawut Morasuk, Ornrat Lohitnavy, Manupat Lohitnavy
BACKGROUND: Clopidogrel is a thienopryridine antiplatelet agent commonly used in the management of cardiovascular diseases. Clopidogrel is metabolized by hepatic CYP2C19 and CYP2B6, therefore, co-administration of clopidogrel and CYP2C19 inhibitors can alter pharmacokinetics of clopidogrel. Omeprazole is a proton pump inhibitor used for decreasing gastric acid production. Omeprazole is known to be a potent inhibitor of CYP2C19. Thus when the drugs are simultaneously administered, clopidogrel plasma concentration levels can be increased...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29057719/changes-in-gefitinib-erlotinib-and-osimertinib-pharmacokinetics-under-various-gastric-ph-levels-following-oral-administration-of-omeprazole-and-vonoprazan-in-rats
#12
Osamu Yasumuro, Shinya Uchida, Yasuharu Kashiwagura, Ayae Suzuki, Shimako Tanaka, Naoki Inui, Hiroshi Watanabe, Noriyuki Namiki
1. Although drug interactions between epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and gastric acid-suppressing medications (AS) are considered clinically significant, there is limited data regarding the influence of various gastric pH conditions on the pharmacokinetics of EGFR-TKIs. We aimed to clarify the changes in the pharmacokinetics of the EGFR-TKIs, gefitinib, erlotinib, and osimertinib, due to the changes in gastric pH after administration of omeprazole or vonoprazan. 2. Omeprazole (10 - 100 mg/kg, p...
October 21, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29052226/translational-high-dimensional-drug-interaction-discovery-and-validation-using-health-record-databases-and-pharmacokinetics-models
#13
Chien-Wei Chiang, Pengyue Zhang, Xueying Wang, Lei Wang, Shijun Zhang, Xia Ning, Li Shen, Sara K Quinney, Lang Li
Polypharmacy increases the risk of drug-drug interactions (DDI's). Combining epidemiological studies with pharmacokinetic modeling, we detected and evaluated high-dimensional DDI's among thirty frequent drugs. Multi-drug combinations that increased risk of myopathy were identified in the FDA Adverse Event Reporting System (FAERS) and electronic medical record (EMR) databases by a mixture drug-count response model. CYP450 inhibition was estimated among the 30 drugs in the presence of 1 to 4 inhibitors using in vitro in vivo extrapolation...
October 20, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29050283/omeprazole-promotes-carcinogenesis-of-fore-stomach-in-mice-with-co-stimulation-of-nitrosamine
#14
Lei Huang, Dong-Jiang Qi, Wei He, A-Man Xu
OBJECTIVES: To investigate if oral omeprazole application induces cancers of fore and glandular stomach in mice. METHODS: A total of 66 eligible male mice were randomly divided into 6 groups, which were treated with control reagent, low (6 mg/kg) and high dose omeprazole (30 mg/kg), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 100 mg/L water), and MNNG plus low and high dose omeprazole, respectively. After 24 weeks, concentrations of acid phosphatase (ACP) and N-acetyl-β-D-glucosaminidase(NAG) in serum and spleen was examined, and p21 and mTOR levels in stomach were detected...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29047048/correction-to-omeprazole-absorption-and-fasting-gastrinemia-after-roux-en-y-gastric-bypass
#15
Renata V A Collares-Pelizaro, José S Santos, Carla B Nonino, Larissa Alves Dos Reis Dias, Cristiane M Gaitani, Wilson Salgado
Larissa Alves dos Reis Dias wasmistakenly included in the 13 acknowledgment section of this article, and was mistakenly.
October 18, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/29045287/yosprala%C3%A2-a-fixed-dose-combination-of-aspirin-and-omeprazole
#16
Keith T Veltri
Cardiovascular disease is the leading cause of morbidity and mortality in the United States. Patients who survive a primary cerebrovascular or cardiovascular event are at increased risk of a subsequent occurrence. Antiplatelet therapy plays an essential role for secondary prevention in individuals with stroke, transient ischemic attack, acute or chronic artery disease or peripheral arterial disease. Maintaining high risk patients on low dose aspirin therapy is a fundamental component of management. However, poor adherence, secondary to the drug's gastrointestinal side effects, has been associated with negative cardiovascular outcomes...
October 17, 2017: Cardiology in Review
https://www.readbyqxmd.com/read/29034770/association-with-polymorphic-marmoset-cytochrome-p450-2c19-of-in-vivo-hepatic-clearances-of-chirally-separated-r-omeprazole-and-s-warfarin-using-individual-marmoset-physiologically-based-pharmacokinetic-models
#17
Takashi Kusama, Akiko Toda, Makiko Shimizu, Shotaro Uehara, Takashi Inoue, Yasuhiro Uno, Masahiro Utoh, Erika Sasaki, Hiroshi Yamazaki
1. Simulated clearances of R-warfarin and efavirenz were recently reported for individual cynomolgus monkeys genotyped for cytochrome P450 2C19 and 2C9, respectively. To expand and verify this modeling procedure, simulations of R/S-omeprazole and R/S-warfarin clearances after oral administrations in individual marmosets were performed using individual simplified physiologically based pharmacokinetic (PBPK) modeling consisting of gut, liver, and central compartments. 2. Pharmacokinetics of R/S-omeprazole were chirally determined using the previously reported plasma microsamples in this study...
October 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29033601/urine-metabolic-ratio-of-omeprazole-in-relation-to-cyp2c19-polymorphisms-in-russian-peptic-ulcer-patients
#18
Natalia P Denisenko, Dmitriy A Sychev, Zhanna M Sizova, Valeriy V Smirnov, Kristina A Ryzhikova, Zhannet A Sozaeva, Elena A Grishina
BACKGROUND: CYP2C19 is known to be the main enzyme of biotransformation of proton pump inhibitors (PPIs), whereas the CYP2C19 gene is highly polymorphic. Genotyping and phenotyping together represent more reliable data about patient's CYP2C19 activity. PURPOSE: The aim of the study was to investigate the applicability of urine metabolic ratio of omeprazole for CYP2C19 phenotyping in Russian peptic ulcer patients with different CYP2C19 genotypes. PATIENTS AND METHODS: A total of 59 patients (19 men and 40 women) aged 18-91 years (mean age 53...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/29024542/the-relative-bioavailability-food-effect-and-drug-interaction-with-omeprazole-of-momelotinib-tablet-formulation-in-healthy-subjects
#19
Yan Xin, Lixin Shao, Julie Maltzman, Dimitrios Stefanidis, Jeffrey Hemenway, Thomas Tarnowski, Wei Deng, Jeffrey A Silverman
Momelotinib is a potent and selective small-molecule inhibitor of JAK1/2 that is under investigation for the treatment of myeloproliferative neoplasms. In a phase 1/2 study in myelofibrosis patients, once-daily dosing of a 300-mg momelotinib capsule was selected for further development based on a favorable benefit:risk profile. A tablet formulation was recently developed for further clinical evaluation. In this study, the relative bioavailability of the tablet formulation versus the initial capsule formulation and the effect of food and omeprazole on the pharmacokinetics of a single-dose momelotinib tablet were evaluated in healthy subjects...
October 11, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29024410/eight-weeks-of-omeprazole-20-mg-significantly-reduces-both-laryngopharyngeal-reflux-and-comorbid-chronic-rhinosinusitis-signs-and-symptoms-randomised-double-blind-placebo-controlled-trial
#20
S A Anzić, M Turkalj, A Župan, M Labor, D Plavec, T Baudoin
OBJECTIVES: Gastroesophageal reflux recommended treatment (dose and duration) with proton-pump inhibitor (PPI) compared to placebo significantly reduces the signs and symptoms of laryngopharyngeal reflux (LPR) and comorbid chronic rhinosinusitis (CRS). DESIGN: Double-blind randomised placebo-controlled trial. SETTING: Eight weeks of treatment with omeprazole 20 mg once daily (OD). PARTICIPANTS: Sixty patients (28 women, aged 19-87 years) with diagnosed LPR and comorbid CRS...
October 11, 2017: Clinical Otolaryngology
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