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https://www.readbyqxmd.com/read/28437284/a-retrospective-study-on-mycophenolic-acid-drug-interactions-effect-of-prednisone-sirolimus-and-tacrolimus-with-mpa
#1
Ana Catalina Alvarez-Elías, Elisa Catherine Yoo, Ekaterina Kirilova Todorova, Ram Nivas Singh, Guido Filler
Mycophenolic acid (MPA), the active compound of mycophenolate mofetil (MMF), is widely used as an antirejection drug following renal transplantation. There is growing evidence supporting the notion that there is substantial variability in the intra- and inter-patient exposure to MPA. Drug interactions involving MPA with tacrolimus, steroids, and sirolimus have been understudied. The objective of this study was to determine the relationship between MPA, steroids, tacrolimus, and sirolimus. MPA trough concentrations from 37 pediatric renal transplant recipients (mean age 7...
April 6, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28435142/clinical-drug-drug-interaction-evaluations-to-inform-drug-use-and-enable-drug-access
#2
Dinko Rekić, Kellie S Reynolds, Ping Zhao, Lei Zhang, Kenta Yoshida, Madhav Sachar, Micheline Piquette Miller, Shiew-Mei Huang, Issam Zineh
Clinical drug-drug interactions (DDIs) can occur when multiple drugs are taken by the same patient. Significant DDIs can result in clinical toxicity or treatment failure. Therefore, DDI assessment is an integral part of drug development and the benefit-risk assessment of new therapies. Regulatory agencies including the Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Pharmaceuticals and Medical Devices Agency of Japan (PMDA) have made recommendations in their DDI guidance documents on various methodologies (in vitro, in silico and clinical) to assess DDI potential and inform patient management strategies...
April 20, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28424965/assessment-of-drug-drug-interaction-potential-between-ceritinib-and-proton-pump-inhibitors-in-healthy-subjects-and-in-patients-with-alk-positive-non-small-cell-lung-cancer
#3
Yvonne Y Lau, Wen Gu, Tiffany Lin, Kalyanee Viraswami-Appanna, Can Cai, Jeffrey W Scott, Michael Shi
PURPOSE: The impact of proton pump inhibitors (PPIs) on the pharmacokinetics (PK) and efficacy of ceritinib was evaluated. METHODS: A healthy subject drug-drug interaction (DDI) study was conducted to assess the effect of esomeprazole on the PK of a single 750 mg dose of ceritinib. To further investigate the impact of PPIs on the PK and efficacy of ceritinib in ALK-positive cancer patients, two subgroup analyses were performed. Analysis 1 evaluated ceritinib steady-state trough concentration (Ctrough,ss) and overall response rate (ORR) by concomitant use of PPIs in patients from the ASCEND-1, -2, and -3 studies; analysis 2 evaluated ceritinib single-dose and steady-state AUC0-24h and C max by concomitant PPI use in patients from ASCEND-1 using a definition of PPI usage similar to that used in the healthy subject study...
April 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28422961/characterization-of-the-mechanism-of-drug-drug-interactions-from-pubmed-using-mesh-terms
#4
Yin Lu, Bryan Figler, Hong Huang, Yi-Cheng Tu, Ju Wang, Feng Cheng
Identifying drug-drug interaction (DDI) is an important topic for the development of safe pharmaceutical drugs and for the optimization of multidrug regimens for complex diseases such as cancer and HIV. There have been about 150,000 publications on DDIs in PubMed, which is a great resource for DDI studies. In this paper, we introduced an automatic computational method for the systematic analysis of the mechanism of DDIs using MeSH (Medical Subject Headings) terms from PubMed literature. MeSH term is a controlled vocabulary thesaurus developed by the National Library of Medicine for indexing and annotating articles...
2017: PloS One
https://www.readbyqxmd.com/read/28417459/does-obesity-complicate-regional-anesthesia-and-result-in-longer-decision-to-delivery-time-for-emergency-cesarean-section
#5
A J Väänänen, J P Kainu, H Eriksson, M Lång, A Tekay, J Sarvela
BACKGROUND: Maternal obesity can cause problems with anesthesia and surgery which may be reflected in emergency cesarean sections (CS) as an increased decision-to-delivery interval (DDI). AIM: To study the association of elevated maternal BMI with DDI and the failure of regional anesthesia. METHODS: Eight hundred and forty-two consecutive emergency CSs during a period of 1 year in a tertiary hospital were studied retrospectively. DDIs were analyzed in Crash and < 30-min urgency categories (n = 528), while the time required to establish regional anesthesia and its success were analyzed for all emergency CS cases...
April 17, 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/28417027/decision-to-delivery-time-intervals-in-emergency-caesarean-section-cases-repeated-cross-sectional-study-from-oman
#6
Kaukab Tashfeen, Malini Patel, Ilham M Hamdi, Ibrahim H A Al-Busaidi, Mansour N Al-Yarubi
OBJECTIVES: In cases of fetal intolerance to labour, meeting the standard decision-to-delivery time interval (DDI) of ≤30 minutes is challenging. This study aimed to assess DDIs in emergency Caesarean section (CS) cases to identify factors causing DDI delays and the impact of a delayed DDI on perinatal outcomes. METHODS: This repeated cross-sectional study included all emergency CS procedures performed due to acute fetal distress, antepartum haemorrhage or umbilical cord prolapse at the Nizwa Hospital, Nizwa, Oman...
February 2017: Sultan Qaboos University Medical Journal
https://www.readbyqxmd.com/read/28416420/identification-of-endogenous-biomarkers-to-predict-the-propensity-of-drug-candidates-to-cause-hepatic-or-renal-transporter-mediated-ddis
#7
REVIEW
Xiaoyan Chu, Grace Hoyee Chan, Raymond Evers
Drug transporters expressed in liver and kidney play a critical role in the elimination of a wide range of drugs and xenobiotics and inhibition of these transporters may therefore cause clinically significant drug-drug interactions (DDIs). Currently, in vitro transporter inhibition data are used to assess the risk that a drug candidate may act as an inhibitor of a transporter in patients at clinically relevant exposures. However, this approach is hampered by low confidence in in vitro to in vivo extrapolations, and large inter-system and inter-lab variability in in vitro data...
April 14, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28414144/intestinal-drug-interactions-mediated-by-oatps-a-systematic-review-of-pre-clinical-and-clinical-findings
#8
REVIEW
Jingjing Yu, Zhu Zhou, Jessica Tay-Sontheimer, René H Levy, Isabelle Ragueneau-Majlessi
In recent years, an increasing number of clinical drug-drug interactions (DDIs) have been attributed to inhibition of intestinal organic anion transporting polypeptides (OATPs); however, only a few of these DDI results were reflected in drug labels. This review aims to provide a thorough analysis of intestinal OATP-mediated pharmacokinetic-based DDIs, using both in vitro and clinical investigations, highlighting the main mechanistic findings and discussing their clinical relevance. On the basis of pharmacogenetic and clinical DDI results, a total of 12 drugs were identified as possible clinical substrates of OATP2B1 and/or OATP1A2...
April 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28413274/evaluation-of-decision-to-delivery-interval-in-emergency-cesarean-section-a-1-year-prospective-audit-in-a-tertiary-care-hospital
#9
Sunanda Gupta, Udita Naithani, C Madhanmohan, Ajay Singh, Pradeep Reddy, Apoorva Gupta
BACKGROUND AND AIMS: The American College of Obstetricians and Gynecologists (ACOG) committee on professional standards and the National Institute of Clinical Excellence (NICE) guidelines suggest that decision-to-delivery interval (DDI) and emergency cesarean section (CS) should not be more than 30 min, and a delay of more than75 min in the presence of maternal or fetal compromise can lead to poor outcome. This prospective 1-year study was conducted on emergency CS in a tertiary care hospital to evaluate the DDI, factors affecting it and to analyze their effects on maternal and neonatal outcome...
January 2017: Journal of Anaesthesiology, Clinical Pharmacology
https://www.readbyqxmd.com/read/28412023/precise-prediction-of-activators-for-the-human-constitutive-androstane-receptor-using-structure-based-three-dimensional-quantitative-structure-activity-relationship-methods
#10
Harutoshi Kato, Noriyuki Yamaotsu, Norihiko Iwazaki, Shigeaki Okamura, Toshiyuki Kume, Shuichi Hirono
The constitutive androstane receptor (CAR, NR1I3) regulates the expression of numerous drug-metabolizing enzymes and transporters. The upregulation of various enzymes, including CYP2B6, by CAR activators is a critical problem leading to clinically severe drug-drug interactions (DDIs). To date, however, few effective computational approaches for identifying CAR activators exist. In this study, we aimed to develop three-dimensional quantitative structure-activity relationship (3D-QSAR) models to predict the CAR activating potency of compounds emerging in the drug-discovery process...
February 9, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28411400/physiologically-based-pharmacokinetic-modeling-suggests-limited-drug-drug-interaction-between-clopidogrel-and-dasabuvir
#11
Mohamad Shebley, Wentao Fu, Prajakta Badri, Daniel A J Bow, Volker Fischer
Dasabuvir, a non-nucleoside NS5B polymerase inhibitor, is a sensitive substrate of cytochrome P450 (CYP) 2C8 with a potential for drug-drug interaction (DDI) with clopidogrel. A physiologically-based pharmacokinetic (PBPK) model was developed for dasabuvir to evaluate the DDI potential with clopidogrel, the acyl-β-D glucuronide metabolite of which has been reported as a strong mechanism-based inhibitor of CYP2C8 based on an interaction with repaglinide. In addition the PBPK model for clopidogrel and its metabolite were updated with additional in vitro data...
April 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28408803/drug-drug-interaction-of-microdose-and-regular-dose-omeprazole-with-a-cyp2c19-inhibitor-and-inducer
#12
Gab-Jin Park, Soo Hyeon Bae, Wan-Su Park, Seunghoon Han, Min-Ho Park, Seok-Ho Shin, Young G Shin, Dong-Seok Yim
PURPOSE: A microdose drug-drug interaction (DDI) study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. PATIENTS AND METHODS: Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim) and known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both studies, the microdose (100 μg, cold compound) and the regular dose (20 mg) of omeprazole were given at days 0 and 1, respectively...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28405956/the-impact-of-polypharmacy-and-drug-interactions-among-the-elderly-population-in-western-sicily-italy
#13
Giulia Scondotto, Fanny Pojero, Sebastiano Pollina Addario, Mauro Ferrante, Maurizio Pastorello, Michele Visconti, Salvatore Scondotto, Alessandra Casuccio
AIM: Primary endpoint was to report polypharmacy distribution in the general population vs ≥65 years old people and to examine the frequency of drug-drug interactions (DDIs) in the Health Local Unit of Palermo, Italy, in relationship with patients' age. METHODS: Drug prescription data for the year 2014 were extracted from the database of the Local Health Unit of Palermo Province, Italy. Patients were divided into five age groups (0-13, 14-64, 65-69, 70-74, and ≥75 year old)...
April 12, 2017: Aging Clinical and Experimental Research
https://www.readbyqxmd.com/read/28401570/effect-of-p-glycoprotein-inhibition-at-the-blood-brain-barrier-on-brain-distribution-of-r-11-c-verapamil-in-elderly-versus-young-subjects
#14
Martin Bauer, Beatrix Wulkersdorfer, Rudolf Karch, Cécile Philippe, Walter Jäger, Johann Stanek, Wolfgang Wadsak, Marcus Hacker, Markus Zeitlinger, Oliver Langer
AIMS: The efflux transporter P-glycoprotein (ABCB1) restricts at the blood-brain barrier (BBB) distribution of many different drugs from blood to the brain. Previous data suggest an age-associated decrease in the expression and function of ABCB1 at the BBB. In this study we investigated the influence of age on the magnitude of an ABCB1-mediated drug-drug interaction (DDI) at the BBB. METHODS: We performed positron emission tomography (PET) scans with the model ABCB1 substrate (R)-[(11) C]verapamil in five young (26 ± 1 years, [mean ± standard deviation]) and five elderly (68 ± 6 years) healthy male volunteers before and after intravenous administration of a low dose of the ABCB1 inhibitor tariquidar (3 mg kg(-1) )...
April 12, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28398958/new-onset-diabetes-in-hiv-treated-adults-from-thailand-predictors-long-term-renal-and-cardiovascular-outcomes
#15
Opass Putcharoen, Lalita Wattanachanya, Jiratchaya Sophonphan, Sarawut Siwamogsatham, Vorapot Sapsirisavat, Sivaporn Gatechompol, Supalak Phonphithak, Stephen J Kerr, Yingyos Avihingsanon, Kiat Ruxrungtham, Anchalee Avihingsanon
OBJECTIVE: To determine the incidence and risk factors for developing diabetes mellitus (DM) in a cohort of Thai HIV-infected patients on long-term combination antiretroviral therapy (cART). DESIGN: Prospective study conducted between July 1996-April 30, 2015. METHODS: 1,748 subjects (60% males) who did not have DM prior to ART were assessed twice a year. Incident DM was defined as either having two consecutive fasting glucose levels >126 mg/dL, or reporting anti-DM medication/ DM diagnosis after starting cART...
April 10, 2017: AIDS
https://www.readbyqxmd.com/read/28396546/structural-insights-into-hiv-reverse-transcriptase-mutations-q151m-and-q151m-complex-that-confer-multi-nucleoside-drug-resistance
#16
Kalyan Das, Sergio E Martinez, Eddy Arnold
HIV-1 reverse transcriptase (RT) is targeted by multiple drugs. RT mutations emerge that confer resistance to nucleoside RT inhibitors (NRTIs) in clinical use. Q151M, and four associated mutations A62V, V75I, F77L, and F116Y were detected in patients failing therapies to dideoxynucleosides (didanosine, ddI; zalcitabine, ddC) and/or zidovudine (AZT). The cluster of the five mutations is referred to as the Q151M complex (Q151Mc), and an RT or virus containing Q151Mc exhibits resistance to multiple NRTIs. To understand the structural basis for Q151M and Q151Mc resistance, we have systematically determined crystal structures of wild-type RT/dsDNA/dATP (I), wild-type RT/dsDNA/ddATP (II), Q151M RT/dsDNA/dATP (III), Q151Mc RT/dsDNA/dATP (IV), and Q151Mc RT/dsDNA/ddATP (V) ternary complexes...
April 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28389457/reviewing-concomitant-medications-for-participants-in-oncology-clinical-trials
#17
Kayla E McGahey, Glen J Weiss
PURPOSE: The importance and key components of clinical medication reviews for participants in oncology clinical trials are described, and drug- drug interactions (DDIs) associated with new oncology drug classes are discussed. SUMMARY: Use of investigational drugs is a mainstay of adult oncology clinical trials and has led to discovery of new oncology drug classes, including immunotherapy agents and oral targeted therapies, as well as novel chemotherapy delivery methods...
April 15, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28385544/a-prediction-method-for-p-glycoprotein-mediated-drug-drug-interactions-at-the-human-blood-brain-barrier-from-blood-concentration-time-profiles-validated-with-pet-data
#18
Akihiro Matsuda, Rudolf Karch, Martin Bauer, Alexander Traxl, Markus Zeitlinger, Oliver Langer
The purpose of this study was to establish physiologically based pharmacokinetic (PBPK) models to predict in humans the brain concentration-time profiles and P-glycoprotein (Pgp)-mediated brain drug-drug interactions (DDIs) between the model Pgp substrate (R)-[(11)C]verapamil (VPM), the model dual Pgp/breast cancer resistance protein (BCRP) substrate [(11)C]tariquidar (TQD) and the Pgp inhibitor tariquidar. The model predictions were validated with results from positron emission tomography (PET) studies in humans...
April 3, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28382584/a-survey-of-attitudes-practices-and-knowledge-regarding-drug-drug-interactions-among-medical-residents-in-iran
#19
Ehsan Nabovati, Hasan Vakili-Arki, Zhila Taherzadeh, Mohammad Reza Saberi, Ameen Abu-Hanna, Saeid Eslami
Background When prescribing medications, physicians should recognize clinically relevant potential drug-drug interactions (DDIs). To improve medication safety, it is important to understand prescribers' knowledge and opinions pertaining to DDIs. Objective To determine the current DDI information sources used by medical residents, their knowledge of DDIs, their opinions about performance feedback on co-prescription of interacting drugs. Setting Academic hospitals of Mashhad University of Medical Sciences (MUMS) in Iran...
April 5, 2017: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/28376709/using-structural-knowledge-in-the-protein-data-bank-to-inform-the-search-for-potential-host-microbe-protein-interactions-in-sequence-space-application-to-mycobacterium-tuberculosis
#20
Gaurang Mahajan, Shekhar C Mande
BACKGROUND: A comprehensive map of the human-M. tuberculosis (MTB) protein interactome would help fill the gaps in our understanding of the disease, and computational prediction can aid and complement experimental studies towards this end. Several sequence-based in silico approaches tap the existing data on experimentally validated protein-protein interactions (PPIs); these PPIs serve as templates from which novel interactions between pathogen and host are inferred. Such comparative approaches typically make use of local sequence alignment, which, in the absence of structural details about the interfaces mediating the template interactions, could lead to incorrect inferences, particularly when multi-domain proteins are involved...
April 4, 2017: BMC Bioinformatics
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