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https://www.readbyqxmd.com/read/28089686/simulations-of-cytochrome-p450-3a4-mediated-drug-drug-interactions-by-simple-two-compartment-model-assisted-static-method
#1
Katsumi Iga, Akiko Kiriyama
In order to predict cytochrome P450 3A4 (CYP3A4)-mediated drug-drug interactions (DDIs), a simple two-compartment model assisted, overall inhibition-activity (Ai, overall) method was derived based upon two concepts. One concept was that the increase in blood victim-level and fold increase in the area under the blood victim-level curve (AUCR) produced by DDI are determined entirely by Ai, overall, the hepatic availability of the victim and fraction of urinary excreted unchanged victim, where Ai, overall is determined by the perpetrator-specific CYP isoform inhibition activities (Ai,CYPs, DDI predictor-1) and victim-specific fractional CYP isoform contributions (fm,CYPs, predictor-2)...
January 12, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28089685/evaluation-of-drug-drug-interaction-potential-between-sacubitril-valsartan-lcz696-and-statins-using-a-physiologically-based-pharmacokinetic-model
#2
Wen Lin, Tao Ji, Heidi Einolf, Surya Ayalasomayajula, Tsu-Han Lin, Imad Hanna, Tycho Heimbach, Christopher Breen, Venkateswar Jarugula, Handan He
Sacubitril/valsartan (LCZ696) has been approved for the treatment of heart failure. Sacubitril is an in vitro inhibitor of OATPs. In clinical studies, LCZ696 increased atorvastatin Cmax by 1.7-fold and AUC by 1.3-fold, but had little or no effect on simvastatin or simvastatin acid exposure. A PBPK modelling approach was applied to explore the underlying mechanisms behind the statin-specific LCZ696 drug interaction observations. The model incorporated OATP-mediated clearance (CLint,T) for simvastatin and simvastatin acid to successfully describe the PK profiles of either analyte in the absence or presence of LCZ696...
January 12, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28074396/target-mediated-drug-disposition-with-drug-drug-interaction-part-ii-competitive-and-uncompetitive-cases
#3
Gilbert Koch, William J Jusko, Johannes Schropp
We present competitive and uncompetitive drug-drug interaction (DDI) with target mediated drug disposition (TMDD) equations and investigate their pharmacokinetic DDI properties. For application of TMDD models, quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are necessary to reduce the number of parameters. To realize those approximations of DDI TMDD models, we derive an ordinary differential equation (ODE) representation formulated in free concentration and free receptor variables. This ODE formulation can be straightforward implemented in typical PKPD software without solving any non-linear equation system arising from the QE or QSS approximation of the rapid binding assumptions...
January 10, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28074395/target-mediated-drug-disposition-with-drug-drug-interaction-part-i-single-drug-case-in-alternative-formulations
#4
Gilbert Koch, William J Jusko, Johannes Schropp
Target-mediated drug disposition (TMDD) describes drug binding with high affinity to a target such as a receptor. In application TMDD models are often over-parameterized and quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are essential to reduce the number of parameters. However, implementation of such approximations becomes difficult for TMDD models with drug-drug interaction (DDI) mechanisms. Hence, alternative but equivalent formulations are necessary for QE or QSS approximations. To introduce and develop such formulations, the single drug case is reanalyzed...
January 10, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28074281/one-step-cad-cam-titanium-cranioplasty-after-drilling-template-assisted-resection-of-intraosseous-skull-base-meningioma-technical-note
#5
A Carolus, S Weihe, K Schmieder, C Brenke
INTRODUCTION: Cranial defects following intra-osseous tumor removal may be large and require adequate reconstruction. CAD/CAM implants have been used for years to achieve an optimal cosmetic result. The disadvantage is that such implants require a second surgery. A preoperative virtual planning of resection margins and the simultaneously fabrication of the cranioplasty could be a possibility to subsume the steps tumor resection and cosmetic restoration to a single procedure. METHODS: We present two cases of patients with complex intra-osseous spheno-orbital meningioma...
January 10, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28074265/pharmacokinetic-and-exposure-response-analyses-of-pertuzumab-in-combination-with-trastuzumab-and-docetaxel-during-neoadjuvant-treatment-of-her2-%C3%A2-early-breast-cancer
#6
Angelica L Quartino, Hanbin Li, Jin Y Jin, D Russell Wada, Mark C Benyunes, Virginia McNally, Lucia Viganò, Ihsan Nijem, Bert L Lum, Amit Garg
PURPOSE: The NeoSphere trial evaluated pertuzumab in the neoadjuvant setting [early breast cancer (EBC)] with pathological complete response (pCR) as the primary efficacy end point. This analysis of pertuzumab aimed to (1) compare its pharmacokinetics (PK) in patients with EBC versus advanced cancers, (2) to further evaluate PK drug-drug interactions (DDIs) when given in combination with trastuzumab, and (3) to assess the relationship between exposure and efficacy to assess the clinical dosing regimen in the EBC patients...
January 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28070719/sunitinib-paracetamol-sex-divergent-pharmacokinetics-and-tissue-distribution-drug-drug-interaction-in-mice
#7
Ming Hui Liew, Salby Ng, Chii Chii Chew, Teng Wai Koo, Yun Lee Chee, Evelyn Li-Ching Chee, Pilar Modamio, Cecilia Fernández, Eduardo L Mariño, Ignacio Segarra
The sex-divergent pharmacokinetics and interaction of tyrosine kinase inhibitor sunitinib with paracetamol was evaluated in male and female mice. Mice (control groups) were administered 60 mg/kg PO sunitinib alone or with 200 mg/kg PO paracetamol (study groups). Sunitinib concentration in plasma, brain, kidney and liver were determined and non-compartmental pharmacokinetic analysis performed. Female control mice showed 36% higher plasma sunitinib AUC0→∞, 31% and 27% lower liver and kidney AUC0→∞ and 2...
January 9, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28069721/specific-inhibition-of-the-distribution-of-lobeglitazone-to-the-liver-by-atorvastatin-in-rats-evidence-for-an-roatp1b2-mediated-interaction-in-hepatic-transport
#8
Chang-Soon Yim, Yoo-Seong Jeong, Song-Yi Lee, Wonji Pyeon, Heon-Min Ryu, Jong-Hwa Lee, Kyeong-Ryoon Lee, Han-Joo Maeng, Suk-Jae Chung
CYP enzymes and hOATP1B1 are reported to be involved in the pharmacokinetics of lobeglitazone (LB), a new PPARγ agonist. Atorvastatin (ATV), a substrate for CYP3A and hOATP1B1, is likely to be co-administered with LB in patients with the metabolic syndrome. We report herein on a study of potential interactions between LB and ATV in rats. When LB was IV-administered with ATV, the systemic clearance (CL; 2.67 ± 0.63 mL/min/kg) and volume of distribution at steady-state (Vss; 289 ± 20 mL/kg) for LB remained unchanged, compared to those of LB without ATV (CL, 2...
January 9, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28066147/prediction-of-pharmacokinetics-and-drug-drug-interaction-potential-using-physiologically-based-pharmacokinetic-pbpk-modeling-approach-a-case-study-of-caffeine-and-ciprofloxacin
#9
Min-Ho Park, Seok-Ho Shin, Jin-Ju Byeon, Gwan-Ho Lee, Byung-Yong Yu, Young G Shin
Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28056782/predicting-potential-drug-drug-interactions-by-integrating-chemical-biological-phenotypic-and-network-data
#10
Wen Zhang, Yanlin Chen, Feng Liu, Fei Luo, Gang Tian, Xiaohong Li
BACKGROUND: Drug-drug interactions (DDIs) are one of the major concerns in drug discovery. Accurate prediction of potential DDIs can help to reduce unexpected interactions in the entire lifecycle of drugs, and are important for the drug safety surveillance. RESULTS: Since many DDIs are not detected or observed in clinical trials, this work is aimed to predict unobserved or undetected DDIs. In this paper, we collect a variety of drug data that may influence drug-drug interactions, i...
January 5, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28056398/clinical-outcome-of-myeloid-sarcoma-in-adult-patients-and-effect-of-allogeneic-stem-cell-transplantation-results-from-a-multicenter-survey
#11
Davide Lazzarotto, Anna Candoni, Carla Filì, Fabio Forghieri, Livio Pagano, Alessandro Busca, Giuseppina Spinosa, Maria Elena Zannier, Erica Simeone, Miriam Isola, Erika Borlenghi, Lorella Melillo, Federico Mosna, Federica Lessi, Renato Fanin
INTRODUCTION: Myeloid Sarcoma (MS) is a rare hematologic myeloid neoplasm that can involve any site of the body. It can occur as an exclusively extramedullary form or it can be associated with an acute myeloid leukemia (AML), a chronic myeloproliferative neoplasm (MPN) or a myelodysplastic syndrome (MDS) at onset or at relapse. The rarity of MS does not enable prospective clinical trials and therefore a specific multicenter register can be useful for the clinical and biological studies of this rare disease...
December 20, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28054285/drug-interactions-in-neurocritical-care
#12
Brian Spoelhof, Salia Farrokh, Lucia Rivera-Lara
Drug-drug interactions (DDIs) are common and avoidable complications that are associated with poor patient outcomes. Neurocritical care patients may be at particular risk for DDIs due to alterations in pharmacokinetic profiles and exposure to medications with a high DDI risk. This review describes the principles of DDI pharmacology, common and severe DDIs in Neurocritical care, and recommendations to minimize adverse outcomes. A review of published literature was performed using PubMed by searching for 'Drug Interaction' and several high DDI risk and common neurocritical care medications...
January 4, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28046033/chronic-pain-how-challenging-are-ddis-in-the-analgesic-treatment-of-inpatients-with-multiple-chronic-conditions
#13
Klarissa Siebenhuener, Emmanuel Eschmann, Alexander Kienast, Dominik Schneider, Christoph E Minder, Reinhard Saller, Lukas Zimmerli, Jürg Blaser, Edouard Battegay, Barbara M Holzer
BACKGROUND: Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. METHODS AND FINDINGS: We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients)...
2017: PloS One
https://www.readbyqxmd.com/read/28036200/insecurity-of-detector-device-independent-quantum-key-distribution
#14
Shihan Sajeed, Anqi Huang, Shihai Sun, Feihu Xu, Vadim Makarov, Marcos Curty
Detector-device-independent quantum key distribution (DDI-QKD) held the promise of being robust to detector side channels, a major security loophole in quantum key distribution (QKD) implementations. In contrast to what has been claimed, however, we demonstrate that the security of DDI-QKD is not based on postselected entanglement, and we introduce various eavesdropping strategies that show that DDI-QKD is in fact insecure against detector side-channel attacks as well as against other attacks that exploit devices' imperfections of the receiver...
December 16, 2016: Physical Review Letters
https://www.readbyqxmd.com/read/28031284/drug-drug-interaction-discovery-and-demystification-using-semantic-web-technologies
#15
Adeeb Noor, Abdullah Assiri, Serkan Ayvaz, Connor Clark, Michel Dumontier
OBJECTIVE: To develop a novel pharmacovigilance inferential framework to infer mechanistic explanations for asserted drug-drug interactions (DDIs) and deduce potential DDIs. MATERIALS AND METHODS: A mechanism-based DDI knowledge base was constructed by integrating knowledge from several existing sources at the pharmacokinetic, pharmacodynamic, pharmacogenetic, and multipathway interaction levels. A query-based framework was then created to utilize this integrated knowledge base in conjunction with 9 inference rules to infer mechanistic explanations for asserted DDIs and deduce potential DDIs...
December 28, 2016: Journal of the American Medical Informatics Association: JAMIA
https://www.readbyqxmd.com/read/28027398/physiologically-based-pharmacokinetic-predictions-of-intestinal-bcrp-mediated-effect-of-telmisartan-on-the-pharmacokinetics-of-rosuvastatin-in-humans
#16
Soo Hyeon Bae, Wan-Su Park, Seunghoon Han, Gab-Jin Park, Jongtae Lee, Taegon Hong, Sangil Jeon, Dong-Seok Yim
It was recently reported that the Cmax and AUC of rosuvastatin increases when it is coadministered with telmisartan. The aim of this study was to explore the mechanism of the interaction of telmisartan and rosuvastatin. A full-PBPK model of telmisartan was developed, and the rosuvastatin model in Simcyp (version 15)'s drug library was modified to reflect ethnic differences in rosuvastatin exposure. PK characteristics, including intestinal and hepatic transporter / enzyme specificities of telmisartan and rosuvastatin, were incorporated into the PBPK models to simulate a rosuvastatin (20 mg) - telmisartan (80 mg) multiple dose drug interaction study...
December 27, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28018756/incidence-of-potential-drug-drug-interactions-in-a-limited-and-stereotyped-prescription-setting-comparison-of-two-free-online-pharmacopoeias
#17
Bhaskar Kannan, Amrutha Bindu Nagella, A Sathia Prabhu, Gopalakrishnan M Sasidharan, A S Ramesh, Venkatesh Madhugiri
BACKGROUND: Drug-drug interactions (DDIs) are very common adverse events in health care delivery settings. The use of electronic pharmacopeias can potentially reduce the incidence of DDIs, but they are often thought to be cumbersome to use. This study is aimed at studying the incidence of potential DDIs in a surgical department, where a limited number of drugs are used in stereotyped combinations. We also compared two popular drug compendia in detecting potential DDIs. METHODS: The prescriptions of selected patients were entered into Epocrates® and Medscape® for Android smartphones...
November 22, 2016: Curēus
https://www.readbyqxmd.com/read/28009450/multi-compartment-compliance-aids-in-the-community-the-prevalence-of-potentially-inappropriate-medications
#18
David Counter, Derek Stewart, Joan MacLeod, James S Mclay
AIMS: To assess the prevalence of potentially inappropriate medications (PIM) use in a population of community-based multi-compartment compliance aid (MCA) users in North- Scotland. METHODS: Data for MCAs dispensed by 48 of the 50 community pharmacies in Aberdeen City between 1(st) June to 31(st) October 2014, together with concurrently prescribed medications, patient demographics and Carstairs Index of social deprivation were recorded. Drug-specific quality indicators for PIMs from the Swedish National Board of Health and Welfare were applied and bivariate logistic regression analysis used to assess for associations with demographic variables...
December 23, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28009020/the-relationship-of-cortical-folding-and-brain-arteriovenous-malformations
#19
Manish N Shah, Sarah E Smith, Donna L Dierker, Joseph P Herbert, Timothy S Coalson, Brent S Bruck, Gregory J Zipfel, David C Van Essen, Ralph G Dacey
BACKGROUND: The pathogenesis of human intracranial arteriovenous malformations (AVMs) is not well understood; this study aims to quantitatively assess cortical folding in patients with these lesions. METHODS: Seven adult participants, 4 male and 3 female, with unruptured, surgically unresectable intracranial AVMs were prospectively enrolled in the study, with a mean age of 42.1 years and Spetzler-Martin grade range of II-IV. High-resolution brain MRI T1 and T2 sequences were obtained...
2016: Neurovasc Imaging
https://www.readbyqxmd.com/read/28005438/interactions-of-crizotinib-and-gefitinib-with-organic-anion-transporting-polypeptides-oatp-1b1-oatp1b3-and-oatp2b1-gefitinib-shows-contradictory-interaction-with-oatp1b3
#20
Toshihiro Sato, Hajime Ito, Ayaka Hirata, Takaaki Abe, Nariyasu Mano, Hiroaki Yamaguchi
1. The drug-drug interaction (DDI) mediated by organic anion-transporting polypeptide (OATP)1B1, OATP1B3, and OATP2B1 has a major impact on the hepatic clearance of drugs. The effects of tyrosine kinase inhibitors (TKIs) on OATPs have not been well studied. In the present study, we evaluated the contribution of OATPs to the hepatic uptake of crizotinib and gefitinib and the interaction of those TKIs with OATPs to estimate DDIs. 2. To clarify whether crizotinib and gefitinib were substrates for OATPs, we performed uptake studies...
December 22, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
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