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https://www.readbyqxmd.com/read/28737446/quantitative-in-vitro-phenotyping-and-prediction-of-drug-interaction-potential-of-cyp2b6-substrates-as-victims
#1
Raghava Choudary Palacharla, Ramakrishna Nirogi, Venkatesham Uthukam, Arunkumar Manoharan, Ranjith Kumar Ponnamaneni, Ilayaraja Kalaikadhiban
1. Determination of fm, CYP for a compound is critical to assess the potential risk of a drug candidate as a victim of DDI. Several compounds are identified as CYP2B6 substrates but the fm, CYP2B6 values are not determined quantitatively 2. Two methods of reaction phenotyping, the chemical inhibition method, and metabolism in rCYP enzymes, were used to determine the relative contributions of the enzymes. Chemical inhibition method was also conducted in the presence of BSA (0.5% w/v) 3. The results confirm with the earlier studies concerning the identity of the CYP2B6 enzyme...
July 24, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28716728/cytochrome-p450-3a-selectively-affects-the-pharmacokinetic-interaction-between-erlotinib-and-docetaxel-in-rats
#2
Xuan Qin, Jian Lu, Peili Wang, Peipei Xu, Mingyao Liu, Xin Wang
Erlotinib as a first-line drug is used in non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations, while resistance to this drug will occur after several years of treatment. Therefore, the microtubule disturber docetaxel is introduced as combined regimen in clinical trials. This report investigated the potentials and mechanisms of drug-drug interaction (DDI) between erlotinib and docetaxel using wild type (WT) and Cyp3a1/2 knockout (KO) rats. The erlotinib O-demethylation and docetaxel hydroxylation reactions in the absence or the presence of another drug were analyzed in vitro via the assay of rat liver microsomes...
July 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28716467/clinically-relevant-potential-drug-drug-interactions-among-outpatients-a-nationwide-database-study
#3
Janja Jazbar, Igor Locatelli, Nejc Horvat, Mitja Kos
BACKGROUND: Adverse drug events due to drug-drug interactions (DDIs) represent a considerable public health burden, also in Slovenia. A better understanding of the most frequently occurring potential DDIs may enable safer pharmacotherapy and minimize drug-related problems. OBJECTIVES: The aim of this study was to evaluate the prevalence and predictors of potential DDIs among outpatients in Slovenia. METHODS: An analysis of potential DDIs was performed using health claims data on prescription drugs from a nationwide database...
July 11, 2017: Research in Social & Administrative Pharmacy: RSAP
https://www.readbyqxmd.com/read/28710808/the-application-of-physiologically-based-pharmacokinetic-modelling-to-assess-the-impact-of-antiretroviral-mediated-drug-drug-interactions-on-piperaquine-antimalarial-therapy-during-pregnancy
#4
Olusola Olafuyi, Michael Coleman, Raj K S Badhan
Antimalarial therapy during pregnancy poses important safety concerns due to potential teratogenicity and maternal physiological and biochemical changes during gestation. Piperaquine (PQ) has gained interest for use in pregnancy in response to increasing resistance towards sulfadoxine-pyrimethamine in sub-Saharan Africa. Co-infection with HIV is common in many developing countries, however, little is known about the impact of anti-retroviral (ARV) mediated drug-drug interaction (DDI) on PQ pharmacokinetics during pregnancy...
July 14, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28689442/drug-interactions-in-hiv-infected-patients-treated-for-hepatitis-c
#5
Vicente Soriano, Pablo Labarga, José V Fernandez-Montero, Carmen de Mendoza, Laura Benítez-Gutiérrez, José M Peña, Pablo Barreiro
The introduction of direct-acting antivirals (DAA) has revolutionized the hepatitis C field. Most hepatitis C patients can now be cured, including those coinfected with HIV. However, drug-drug interactions (DDI) between DAA and antiretrovirals (ARV) should be known to prevent either toxicity due to drug overexposure or treatment failures due to low drug concentrations. Areas covered: Clinically significant DDI may be classified as major (when co-administration should be contraindicated) or minor (when they require close monitoring, changes in drug dosage or in timing)...
July 13, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28688108/a-physiologically-based-pharmacokinetic-modeling-approach-to-predict-buprenorphine-pharmacokinetics-following-intravenous-sublingual-administration
#6
Hari V Kalluri, Hongfei Zhang, Steve N Caritis, Raman Venkataramanan
INTRODUCTION: Opioid dependence is associated with high morbidity and mortality. Buprenorphine(BUP) is approved by the FDA to treat opioid dependence. There is a lack of clear consensus on appropriate dosing of BUP due to inter-patient physiological differences in absorption/disposition, subjective response assessment and other patient comorbidities. The objective of this study is to build and validate robust physiologically-based-pharmacokinetic(PBPK) models for intravenous(IV) and Sublingual(SL) BUP as a first-step to optimize BUP pharmacotherapy...
July 8, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28679023/notable-drug-drug-interaction-between-etizolam-and-itraconazole-in-poor-metabolizers-of-cytochrome-p450-2c19
#7
Takehito Yamamoto, Kenichi Furihata, Akihiro Hisaka, Takashi Moritoyo, Kazuaki Ogoe, Shizuko Kusayama, Keiju Motohashi, Akiko Mori, Takeshi Iwatsubo, Hiroshi Suzuki
In this study, impact of a polymorphism of CYP2C19 on drug-drug interaction (DDI) was examined for etizolam. The effect of itraconazole (a strong CYP3A inhibitor) on the pharmacokinetics of etizolam (a substrate of CYP2C19 and CYP3A) was assessed in both extensive metabolizers (EMs) and poor metabolizers (PMs) of CYP2C19. Sixteen participants (8 EMs and 8 PMs) received a single oral dose of etizolam (0.25 mg) on day 1. The participants ingested itraconazole (200 mg twice a day) on days 2-5. On day 5, participants received an oral dose of etizolam (0...
July 5, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28674251/co-administration-of-fluvastatin-and-cyp3a4-and-cyp2c8-inhibitors-may-increase-the-exposure-to-fluvastatin-in-carriers-of-cyp2c9-genetic-variants
#8
Yuji Mukai, Masayuki Narita, Erika Akiyama, Kanami Ohashi, Yasutaka Horiuchi, Yuka Kato, Takaki Toda, Anders Rane, Nobuo Inotsume
Fluvastatin, which is one of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins), is primarily metabolized by CYP2C9 and to a lesser extent by CYP3A4 and CYP2C8. Predictions of drug-drug interactions (DDI) are important for the safety of combination therapies with statins, in particular drugs that are metabolized by CYP3A4. Little information is available regarding drug interactions with fluvastatin. Since CYP2C9 is a polymorphic enzyme, we investigated the effect of DDI via CYP2C9, CYP3A4, and CYP2C8 on fluvastatin pharmacokinetics by using a validated prediction method in relation to CYP2C9 variants...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28665037/prevalence-of-potentially-serious-drug-drug-interactions-among-south-african-elderly-private-health-sector-patients-using-the-mimica-matanovi%C3%A4-vlahovi%C3%A4-pal%C3%A4-evski-protocol
#9
Julandi A van Heerden, Johanita R Burger, Jan J Gerber, Vera Vlahović-Palčevski
OBJECTIVES: To determine the prevalence of potentially serious drug-drug interactions (DDIs) and their relationship with gender and age, among elderly in South Africa. METHODS: A cross-sectional study was conducted using pharmaceutical claims data for 2013, for a total of 103 420 medical scheme beneficiaries' ≥65 years. All medications dispensed within one calendar month where the days' supply of medication dispensed overlapped, were grouped as one prescription...
June 30, 2017: International Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28659246/discovery-of-novel-dapy-ias-hybrid-derivatives-as-potential-hiv-1-inhibitors-using-molecular-hybridization-based-on-crystallographic-overlays
#10
Boshi Huang, Xueshun Wang, Xinhao Liu, Zihui Chen, Wanzhuo Li, Songkai Sun, Huiqing Liu, Dirk Daelemans, Erik De Clercq, Christophe Pannecouque, Peng Zhan, Xinyong Liu
Crystallographic overlap studies and pharmacophoric analysis indicated that diarylpyrimidine (DAPY)-based HIV-1 NNRTIs showed a similar binding mode and pharmacophoric features as indolylarylsulfones (IASs), another class of potent NNRTIs. Thus, a novel series of DAPY-IAS hybrid derivatives were identified as newer NNRTIs using structure-based molecular hybridization. Some target compounds exhibited moderate activities against HIV-1 IIIB strain, among which the two most potent inhibitors possessed EC50 values of 1...
June 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28656193/a-preliminary-review-of-warfarin-toxicity-in-a-tertiary-hospital-in-cape-town-south-africa
#11
Annemarie Jacobs, Fatima Bassa, Eric H Decloedt
AIM: Warfarin is a widely used anticoagulant for the prevention and treatment of thromboembolism. We conducted a retrospective review to determine the causes and management of warfarin toxicity of patients admitted to Tygerberg hospital between June 2014 and June 2015. RESULTS: We identified and evaluated 126 patients who met the inclusion criteria. The cause of warfarin toxicity was identified and addressed in only 14.3% (18/126) of patients. Where the cause was identified, 56% (10/18) was due to dosing errors and 17% (3/18) drug-drug interaction (DDI)...
May 21, 2017: Cardiovascular Journal of Africa
https://www.readbyqxmd.com/read/28650921/effect-of-continuity-of-care-on-drug-drug-interactions
#12
Jiun-Yu Guo, Yiing-Jenq Chou, Christy Pu
BACKGROUND: Drug-drug interaction (DDI) is a critical concern in health care systems because it is directly associated with patient outcomes and is generally preventable. However, few studies have been conducted on whether poor continuity of care (COC) is a determinant of DDIs and whether this effect varies by level of comorbidity. Patients with higher comorbidity normally require more complex treatment regimens than other patients, and hence their COC is more critical for ensuring the accuracy of their medication information...
August 2017: Medical Care
https://www.readbyqxmd.com/read/28650400/high-need-to-switch-cart-or-co-medication-with-the-initiation-of-daas-in-elderly-hiv-hcv-co-infected-patients
#13
Elise J Smolders, Colette Smit, Clara Tmm De Kanter, Anton Dofferhoff, Joop E Arends, Kees Brinkman, Bart Rijnders, Marc Van Der Valk, Peter Reiss, David M Burger
BACKGROUD: To describe the use of non-antiretroviral co-medication and combination antiretroviral therapy (cART) in HIV/hepatitis C virus (HCV) co-infected patients, and to predict the potential for drug-drug interactions (DDIs) with direct-acting antivirals (DAAs) against HCV. METHODS: This is a retrospective, cross-sectional study, using the Dutch nationwide ATHENA observational HIV cohort database. All patients with a known HIV/HCV co-infection on 1 January 2015 were included...
June 22, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28646080/considerations-from-the-iq-induction-working-group-in-response-to-drug-drug-interaction-guidances-from-regulatory-agencies-focus-on-down-regulation-cyp2c-induction-and-cyp2b6-positive-control
#14
Niresh Hariparsad, Diane Ramsden, Jairam Palamanda, Joshua G Dekeyser, Odette A Fahmi, Jane R Kenny, Heidi Einolf, Michael Mohutsky, Magalie Pardon, Amy Y Siu, Liangfu Chen, Michael Sinz, Barry Jones, Robert Walsky, Shannon Dallas, Suresh K Balani, George Zhang, David Buckley, Donald Tweedie
The European Medicines Agency (EMA), the Pharmaceutical and Medical Devices Agency and the Food and Drug Administration have issued guidances for the conduct of drug-drug interaction (DDI) studies. To examine the applicability of these regulatory recommendations specifically for induction, a group of scientists, under the auspices of the Drug Metabolism Leadership Group of the Innovation and Quality (IQ) Consortium, formed the Induction Working Group (WG). A team of 20 scientists, from 16 of the 39 pharmaceutical companies, which are members of the IQ Consortium, and three Contract Research Organizations, reviewed the recommendations, focusing initially on the current EMA guidance...
June 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28628392/potential-drug-drug-and-herb-drug-interactions-in-patients-with-cancer-a-prospective-study-of-medication-surveillance
#15
Allan Ramos-Esquivel, Álvaro Víquez-Jaikel, Cristina Fernández
PURPOSE: Patients with cancer frequently use herbal supplements and concomitant medications along with antineoplastic agents. These patients are at high risk of herb-drug interactions (HDIs) and drug-drug interactions (DDIs). We aimed to determine clinically relevant DDIs and HDIs leading to pharmaceutical intervention. METHODS: Patients starting a new anticancer therapy were asked to complete a questionnaire to identify concomitant use of any over-the-counter drug or herbal supplement...
July 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28623363/machine-learning-workflow-to-enhance-predictions-of-adverse-drug-reactions-adrs-through-drug-gene-interactions-application-to-drugs-for-cutaneous-diseases
#16
Kalpana Raja, Matthew Patrick, James T Elder, Lam C Tsoi
Adverse drug reactions (ADRs) pose critical public health issues, affecting over 6% of hospitalized patients. While knowledge of potential drug-drug interactions (DDI) is necessary to prevent ADR, the rapid pace of drug discovery makes it challenging to maintain a strong insight into DDIs. In this study, we present a novel literature-mining framework for enhancing the predictions of DDIs and ADR types by integrating drug-gene interactions (DGIs). The ADR types were adapted from a DDI corpus, including i) adverse effect; ii) effect at molecular level; iii) effect related to pharmacokinetics; and iv) DDIs without known ADRs...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28605776/exploring-convolutional-neural-networks-for-drug-drug-interaction-extraction
#17
Víctor Suárez-Paniagua, Isabel Segura-Bedmar, Paloma Martínez
Drug-drug interaction (DDI), which is a specific type of adverse drug reaction, occurs when a drug influences the level or activity of another drug. Natural language processing techniques can provide health-care professionals with a novel way of reducing the time spent reviewing the literature for potential DDIs. The current state-of-the-art for the extraction of DDIs is based on feature-engineering algorithms (such as support vector machines), which usually require considerable time and effort. One possible alternative to these approaches includes deep learning...
January 1, 2017: Database: the Journal of Biological Databases and Curation
https://www.readbyqxmd.com/read/28601113/attractor-dynamics-of-dyadic-interaction-a-recurrence-based-analysis
#18
Marlenny Guevara, Ralf F A Cox, Marijn van Dijk, Paul van Geert
The aim of this study was to investigate interpersonal coordination in young children during dyadic problem solving, by using Cross-Recurrence Quantification Analysis (CRQA). We examined the interactions of seven dyads of children (Mage= 5.1 years) in a longitudinal design (6 sessions) with a sequence of problem-solving tasks increasing in difficulty. An innovative implementation of CRQA is presented in order to study the attractor dynamics of dyadic coordination. The analysis consisted of distinguishing two recurrent states in the relationship between children and the task...
July 2017: Nonlinear Dynamics, Psychology, and Life Sciences
https://www.readbyqxmd.com/read/28595649/data-driven-prediction-of-adverse-drug-reactions-induced-by-drug-drug-interactions
#19
Ruifeng Liu, Mohamed Diwan M AbdulHameed, Kamal Kumar, Xueping Yu, Anders Wallqvist, Jaques Reifman
BACKGROUND: The expanded use of multiple drugs has increased the occurrence of adverse drug reactions (ADRs) induced by drug-drug interactions (DDIs). However, such reactions are typically not observed in clinical drug-development studies because most of them focus on single-drug therapies. ADR reporting systems collect information on adverse health effects caused by both single drugs and DDIs. A major challenge is to unambiguously identify the effects caused by DDIs and to attribute them to specific drug interactions...
June 8, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28570369/drug-interactions-and-the-role-of-pharmacokinetic-trials-in-guiding-choices-in-first-line-hiv-therapy-in-low-income-and-middle-income-countries
#20
Kay Seden, Marta Boffito, Saye Khoo
PURPOSE OF REVIEW: Low- and middle-income countries (LMICs) face specific challenges in the treatment of people living with HIV. Drug-drug interactions (DDIs) involving antiretrovirals (ARVs) are prevalent in all settings and have considerable potential to cause clinical harm to patients via toxicity or reduced efficacy of treatment. Differing comorbidities, endemic infections and traditional medicines may complicate ARV therapy (ART) in LMICs, which usually takes a public health approach in these settings, with fewer alternative regimens available...
July 2017: Current Opinion in HIV and AIDS
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