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https://www.readbyqxmd.com/read/28628392/potential-drug-drug-and-herb-drug-interactions-in-patients-with-cancer-a-prospective-study-of-medication-surveillance
#1
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...
June 19, 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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28552429/prediction-of-renal-transporter-mediated-drug-drug-interactions-for-a-drug-which-is-an-oat-substrate-and-inhibitor-using-pbpk-modelling
#7
Kathryn Ball, Tanguy Jamier, Yannick Parmentier, Claire Denizot, Agnes Mallier, Marylore Chenel
A PBPK modelling approach was used to predict organic anion transporter (OAT) mediated drug-drug interactions involving S44121, a substrate and an inhibitor of OAT1 and OAT3. Model predictions were then compared to the results of a clinical DDI study which was carried out to investigate the interaction of S44121 with probenecid, tenofovir and ciprofloxacin. PBPK models were developed and qualified using existing clinical data, and inhibition constants were determined in vitro. The model predictions for S44121 as an OAT inhibitor were similar to the results obtained from the clinical DDI study, with no interaction observed for tenofovir or ciprofloxacin in the presence of S44121...
May 25, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28550055/potential-drug-interactions-mediated-by-renal-organic-anion-transporter-oatp4c1
#8
Toshihiro Sato, Eikan Mishima, Nariyasu Mano, Takaaki Abe, Hiroaki Yamaguchi
OATP4C1 is an organic anion transporter expressed in the basolateral membrane of the renal proximal tubules. It plays a major role in the urinary excretion of both exogenous drugs and endogenous compounds. Our previous studies have indicated the importance of OATP4C1 in pathological and physiological conditions; however, the majority of its pharmacological characteristics remained unclear. Therefore, to provide essential information for clinical drug therapy decisions and drug development, we, in this study, attempted to clarify drug interactions mediated by OATP4C1...
May 26, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28548030/everolimus-inhibited-multiple-isoforms-of-udp-glucuronosyltransferases-ugts
#9
Zuo Du, Guang Wang, Yun-Feng Cao, Cui-Min Hu, Kun Yang, Yong-Zhe Liu, Chun-Ze Zhang, Wei-Hua Zhang, Zhi-Tu Zhu, Hong-Zhi Sun, Xiao-Yu Sun, Mo Hong, Zhong-Ze Fang
1. Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) and has been clinically utilized to prevent the rejection of organ transplants. This study aims to determine the inhibition of everolimus on the activity of phase II drug-metabolizing enzymes UDP-glucuronosyltransferases (UGTs). 2. The results showed that 100 uM of everolimus exerted more than 80% inhibition towards UGT1A1, -1A3, and -2B7. UGT1A3 and UGT2B7 were selected to elucidate the inhibition mechanism, and in silico docking showed that hydrogen bonds and hydrophobic interactions mainly contributed to the strong binding of everolimus towards the activity cavity of UGT1A3 and UGT2B7...
May 26, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28546104/development-of-a-paediatric-physiologically-based-pharmacokinetic-model-to-assess-the-impact-of-drug-drug-interactions-in-tuberculosis-co-infected-malaria-subjects-a-case-study-with-artemether-lumefantrine-and-the-cyp3a4-inducer-rifampicin
#10
Olusola Olafuyi, Michael Coleman, Raj K S Badhan
The fixed dosed combination of artemether and lumefantrine (AL) is widely used for the treatment of malaria in adults and children in sub-Sahara Africa, with lumefantrine day 7 concentrations being widely used as a marker for clinical efficacy. Both are substrates for CYP3A4 and susceptible to drug-drug interactions (DDIs); indeed, knowledge of the impact of these factors is currently sparse in paediatric population groups. Confounding malaria treatment is the co-infection of patients with tuberculosis. The concomitant treatment of AL with tuberculosis chemotherapy, which includes the CYP3A4 inducer rifampicin, increases the risk of parasite recrudescence and malaria treatment failure...
May 22, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28538045/donor-derived-infections-in-solid-organ-transplant-patients-toward-a-holistic-approach
#11
Esther Benamu, Cameron R Wolfe, Jose G Montoya
PURPOSE OF REVIEW: Solid organ demand far exceeds organ supply. Strategies to increase the donor pool include the liberalization of selection criteria without increasing the risk of unexpected donor-derived infection (DDI), a rare complication of transplantation carrying high morbidity and mortality. We review the challenging aspects in the prevention of DDI, focusing on the complexities of data sharing and efficient communication and the role infectious diseases specialists play in the process...
May 19, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28535410/effect-of-enzyme-inhibition-on-perampanel-pharmacokinetics-why-study-design-matters
#12
Barry E Gidal, Rama Maganti, Antonio Laurenza, Haichen Yang, David A Verbel, Edgar Schuck, Jim Ferry
OBJECTIVES: Perampanel, a selective, noncompetitive AMPA receptor antagonist, is indicated as adjunctive therapy for the treatment of partial seizures with or without secondarily generalized seizures and primary generalized tonic-clonic seizures in patients with epilepsy aged 12years and older. In vitro studies and Phase I trials indicate that perampanel is metabolized almost exclusively by CYP3A, with an elimination half-life (t1/2) averaging approximately 105h. Understanding of pharmacokinetic (PK) interactions-enzyme inhibition or induction-and anticipating their occurrence are important for management of patients with epilepsy...
April 26, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28513856/the-utility-of-a-population-approach-in-drug-drug-interaction-assessments-a-simulation-evaluation
#13
Diane D Wang, Yanke Yu, Nastya Kassir, Min Zhu, William D Hanley, Justin C Earp, Andrew T Chow, Manish Gupta, Chuanpu Hu
This study aims at evaluating the utility of the population pharmacokinetics approach in therapeutic protein drug-drug-interaction (DDI) assessment. Simulations were conducted for 2 representative victim drugs, methotrexate and trastuzumab, using a parallel-group design with and without the interaction drug. The effect of a perpetrator on the exposure of the victim drug is described as the ratio of clearance/apparent clearance of the victim drug given with or without the perpetrator. The power of DDI assessment was calculated as the percentage of runs with 90% confidence interval of the estimated DDI effect within 80% to 125% for the scenarios of no DDI, benchmarked with the noncompartmental approach with intensive sampling...
May 17, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28511403/a-prospective-analysis-of-drug-interactions-in-patients-of-intensive-cardiac-care-unit
#14
Shipra Jain, Pushpawati Jain, Kopal Sharma, Pushpendra Saraswat
INTRODUCTION: Drug-Drug Interaction (DDI) is a serious concern in cardiac patients due to polypharmacy. AIM: The present study was aimed to identify the potential DDI among hospitalized cardiac patients and evaluate the mechanism and severity of such interactions. MATERIALS AND METHODS: A prospective observational study was conducted in intensive cardiac care unit of a tertiary care hospital for six months. Patients aged 18 years and above and taking two or more drugs were included in the study...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28503751/in-vitro-evaluation-of-potential-transporter-mediated-drug-interactions-of-evogliptin
#15
Dae Y Lee, Hye W Chae, Hyunjoo Shim
To date, little is known about the transporter-mediated drug-drug interaction (DDI) potential of evogliptin, a novel DPP-4 inhibitor. The objective of this study was to evaluate the DDI potential of evogliptin using various in vitro assays in transporter-expressing cell lines. After incubating evogliptin with cells overexpressing OAT1, OAT3, OCT2, OATP1B1, and OATP1B3, there was no notable cellular accumulation of evogliptin (fold accumulation, 0.41-1.86). In bidirectional transport assays using Caco-2 cell monolayer, a high efflux ratio (ER, 522) of evogliptin was observed, which was significantly decreased (97...
May 14, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28495568/quantitative-analyses-of-the-influence-of-parameters-governing-rate-determining-process-of-hepatic-elimination-of-drugs-on-the-magnitudes-of-drug-drug-interactions-via-hepatic-oatps-and-cyp3a-using-physiologically-based-pharmacokinetic-models
#16
Takashi Yoshikado, Maeda Kazuya, Hiroyuki Kusuhara, Ken-Ichi Furihata, Yuichi Sugiyama
Physiologically-based pharmacokinetic (PBPK) models were constructed for hepatic organic anion transporting polypeptides (OATPs) and cytochrome P450 3A (CYP3A) substrates (bosentan, repaglinide, clarithromycin, and simeprevir), a CYP3A probe substrate (midazolam), and selective inhibitors for OATPs (rifampicin) and CYP3A (itraconazole), though the role of OATPs in the hepatic uptake of clarithromycin is unclear. The pharmacokinetic data were obtained from our previous clinical drug-drug interaction (DDI) study...
May 8, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28489843/-non-cirrhotic-portal-hypertension-due-to-didanosina-a-rare-case
#17
María T Gamero, María Susana Gallardo, Víctor Aguilar, Eduar Bravo, Julissa Guevara, Fernando Mejia
Liver involvement is usually seen in patients infected with the human immunodeficiency virus (HIV), especially in patients coinfected with hepatitis B or C, in alcohol abuse, etc. However, there is a group of patients who develop liver involvement and portal hypertension of unspecified cause. Non-cirrhotic portal hypertension (NCPH) is a liver disorder recently described, but potentially serious. It has been reported in HIV-infected patients with highly active antiretroviral therapy (HAART), specifically didanosine (DDI)...
January 2017: Revista de Gastroenterología del Perú: órgano Oficial de la Sociedad de Gastroenterología del Perú
https://www.readbyqxmd.com/read/28484975/a-clinical-cassette-dosing-study-for-evaluating-the-contribution-of-hepatic-oatps-and-cyp3a-to-drug-drug-interactions
#18
Takashi Yoshikado, Kazuya Maeda, Sawako Furihata, Hanano Terashima, Takeshi Nakayama, Keiko Ishigame, Kazunobu Tsunemoto, Hiroyuki Kusuhara, Ken-Ichi Furihata, Yuichi Sugiyama
PURPOSE: To demonstrate the relative importance of organic anion-transporting polypeptides (OATPs) and cytochrome P450 3A (CYP3A) in the hepatic elimination of substrate drugs. METHODS: A cocktail of subtherapeutic doses of bosentan, repaglinide, clarithromycin, darunavir, simeprevir, and midazolam (CYP3A probe) was administered orally to eight healthy volunteers. Rifampicin (OATP inhibitor; 600 mg, p.o.) and itraconazole (CYP3A inhibitor; 200 mg, i.v.) were coadministered with the cocktail in the second and third phases, respectively...
May 8, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28483778/mechanisms-and-predictions-of-drug-drug-interactions-of-the-hepatitis-c-virus-three-direct-acting-antiviral-regimen-paritaprevir-ritonavir-ombitasvir-and-dasabuvir
#19
Mohamad Shebley, Jinrong Liu, Olga Kavetskaia, Jens Sydor, Sonia M de Morais, Volker Fischer, Marjoleen J M A Nijsen, Daniel A J Bow
To assess drug-drug interaction (DDI) potential for the three direct-acting antiviral (3D) regimen of ombitasvir, dasabuvir, and paritaprevir, in vitro studies profiled drug-metabolizing enzyme and transporter interactions. Using mechanistic static and dynamic models, DDI potential was predicted for CYP3A, CYP2C8, UDP-glucuronosyltransferase (UGT) 1A1, organic anion-transporting polypeptide (OATP) 1B1/1B3, breast cancer resistance protein (BCRP), and P-glycoprotein (P-gp). Perpetrator static model DDI predictions for metabolizing enzymes were within 2-fold of the clinical observations, but additional physiologically based pharmacokinetic modeling was necessary to achieve the same for drug transporters...
July 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28483425/risk-assessment-using-cytochrome-p450-time-dependent-inhibition-assays-at-single-time-and-concentration-in-the-early-stage-of-drug-discovery
#20
Mai Kosaka, Yohei Kosugi, Hideki Hirabayashi
In this article, we proposed a risk assessment strategy for CYP3A time-dependent inhibition (TDI) during drug discovery based on a through retrospective study of 13 reference drugs, some of which are known to have in vitro TDI potential, but have unknown clinical relevance. First, the traditional parameter kinact/KI, recommended by regulatory authorities for necessity decision-making in clinical drug-drug interaction (DDI) studies, was investigated as a predictive index for clinical TDI liability. The cutoff value of 1...
May 5, 2017: Journal of Pharmaceutical Sciences
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