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https://www.readbyqxmd.com/read/29129847/effects-of-ketoconazole-on-cyclophosphamide-metabolism-evaluation-of-cyp3a4-inhibition-effect-using-the-in-vitro-and-in-vivo-models
#1
Le Yang, Chenyang Yan, Feng Zhang, Bo Jiang, Shouhong Gao, Youtian Liang, Lifeng Huang, Wansheng Chen
Cyclophosphamide (CP) is widely used in anticancer therapy regimens and 2-dechloroethylcyclophosphamide (DECP) is its side-chain dechloroethylated metabolite. N-dechloroethylation of CP mediated by the enzyme CYP3A4 yields nephrotoxic and neurotoxic chloroacetaldehyde (CAA) in equimolar amount to DECP. This study aimed to evaluate the inhibitory effect of ketoconazole (KTZ) on CP metabolism through in vitro and in vivo drug-drug interaction (DDI) research. Long-term treatment of KTZ induces hepatic injury; thus single doses of KTZ at low, middle, and high levels (10, 20, and 40 mg/kg) were investigated for pharmacokinetic DDI with CP...
November 13, 2017: Experimental Animals
https://www.readbyqxmd.com/read/29128087/-platelet-rich-plasma-prp-and-disc-lesions-a-review-of-the-literature
#2
REVIEW
L Charneux, C Demoulin, M Vanderthomment, M Tomasella, M-A Ferrara, S Grosdent, S Bethlen, R Fontaine, P Gillet, T Racaru, J-F Kaux
The spine has been the subject of extensive clinical research since it is the source of many painful complaints. However, there is little scientific evidence concerning the therapeutic proposals. During the course of life, the intervertebral disc degenerates, which over time diminishes its damping capacity and facilitates the expulsion of the nucleus pulposus through the annulus fibrosus. The degeneration of the intervertebral disc (DDI) is the origin of some back pain and various specific treatments have been developed...
November 8, 2017: Neuro-Chirurgie
https://www.readbyqxmd.com/read/29123429/assessment-of-prescribed-medications-and-pattern-of-distribution-for-potential-drug-drug-interactions-among-chronic-kidney-disease-patients-attending-the-nephrology-clinic-of-lagos-university-teaching-hospital-in-sub-saharan-west-africa
#3
Olumuyiwa John Fasipe, Peter Ehizokhale Akhideno, Obiyo Nwaiwu, Alex Adedotun Adelosoye
Introduction: Life expectancy has increased significantly among chronic kidney disease (CKD) patients due to the extensive use of polypharmacy practice for medication prescriptions. This predisposes them to potential drug-drug interactions (DDIs), which can lead to an increase in morbidity, mortality, length of hospital stay, and health care cost. Methods: This was a 30-month retrospective study that reviewed the medical case records of consenting adult CKD patients from January 2014 to June 2016...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/29121476/hepatic-transporter-drug-drug-interactions-an-evaluation-of-approaches-and-methodologies
#4
Beth Williamson, Robert J Riley
Drug-drug interactions (DDIs) continue to account for 5% of hospital admissions and therefore remain a major regulatory concern. Effective, quantitative prediction of DDIs will reduce unexpected clinical findings and encourage projects to frontload DDI investigations rather than concentrating on risk management ("manage the baggage") later in drug development. A key challenge in DDI prediction is the discrepancies between reported models. Areas covered: The current synopsis focuses on four recent influential publications on hepatic drug transporter DDIs using static models that tackle interactions with individual transporters and in combination with other drug transporters and metabolising enzymes...
November 9, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29119333/physiologically-based-pharmacokinetic-modelling-of-cytochrome-p450%C3%A2-2c9-related-tolbutamide-drug-interactions-with-sulfaphenazole-and-tasisulam
#5
Everett J Perkins, Maria Posada, P Kellie Turner, Jill Chappell, Wee Teck Ng, Chris Twelves
BACKGROUND AND OBJECTIVES: Cytochrome P450 2C9 (CYP2C9) is involved in the biotransformation of many commonly used drugs, and significant drug interactions have been reported for CYP2C9 substrates. Previously published physiologically based pharmacokinetic (PBPK) models of tolbutamide are based on an assumption that its metabolic clearance is exclusively through CYP2C9; however, many studies indicate that CYP2C9 metabolism is only responsible for 80-90% of the total clearance. Therefore, these models are not useful for predicting the magnitude of CYP2C9 drug-drug interactions (DDIs)...
November 8, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29117990/simultaneous-physiologically-based-pharmacokinetic-pbpk-modeling-of-parent-and-active-metabolites-to-investigate-complex-cyp3a4-drug-drug-interaction-potential-a-case-example-of-midostaurin
#6
Helen Gu, Catherine Dutreix, Sam Rebello, Taoufik Ouatas, Lai Wang, Dung Yu Chun, Heidi J Einolf, Handan He
Midostaurin (PKC412) is being investigated for the treatment of acute myeloid leukemia (AML) and advanced systemic mastocytosis (advSM). It is extensively metabolized by cytochrome P450 (CYP) 3A4 to form 2 major active metabolites, CGP52421 and CGP62221. In vitro and clinical drug-drug interaction (DDI) studies indicated that midostaurin and its metabolites are substrates, reversible and time-dependent inhibitors, and inducers of CYP3A4. A simultaneous pharmacokinetic model of parent and active metabolites was initially developed by incorporating data from in vitro, preclinical, and clinical pharmacokinetic studies in healthy volunteers and in patients with AML or advSM...
November 8, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29117238/tdf-and-quantitative-ultrasound-bone-quality-in-african-patients-on-second-line-art-anrs-12169-2lady-sub-study
#7
Firmin Nongodo Kabore, Sabrina Eymard-Duvernay, Jacques Zoungrana, Stéphanie Badiou, Guillaume Bado, Arsène Héma, Assane Diouf, Eric Delaporte, Sinata Koulla-Shiro, Laura Ciaffi, Amandine Cournil
BACKGROUND: Bone demineralization, which leads to osteoporosis and increased fracture risk, is a common metabolic disorder in HIV-infected individuals. In this study, we aimed to assess the change in bone quality using quantitative ultrasound (QUS) over 96 weeks of follow-up after initiation of second-line treatment, and to identify factors associated with change in bone quality. METHODS AND FINDINGS: In a randomized trial (ANRS 12169), TDF and PI-naïve participants failing standard first-line treatment, from Burkina Faso, Cameroon, and Senegal were randomized to receive either TDF/FTC/LPVr, ABC/ddI/LPVr or TDF/FTC/DRVr...
2017: PloS One
https://www.readbyqxmd.com/read/29112329/in-vitro-and-in-vivo-investigation-of-potential-for-complex-cyp3a-interaction-for-pf-00251802-dagrocorat-a-novel-dissociated-agonist-of-the-glucocorticoid-receptor
#8
Sharon L Ripp, Arnab Mukherjee, Heather Eng, Thomas Stock, Dona Fleishaker, Tina Checchio, Brinda Tammara
The dissociated agonists of the glucocorticoid receptor are a novel class of agents in clinical development for rheumatoid arthritis. PF-04171327 (fosdagrocorat) is a phosphate ester prodrug of PF-00251802 (dagrocorat), a selective high-affinity partial agonist of the glucocorticoid receptor, which is further metabolized to PF-04015475. This study evaluated the cytochrome P450 (CYP)-mediated drug-drug interaction (DDI) potential of PF-00251802 and PF-04015475 in vitro and used model-based prediction approaches to estimate clinical impact...
November 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29111291/-can-we-reduce-the-decision-to-delivery-interval-in-case-of-emergency-cesarean-sections-by-optimizing-the-premises-architecture
#9
A-S Lafitte, D Vardon, R Morello, M Lecerf, Z Stewart, M Dreyfus
OBJECTIVE: To study the influence of architectural premises' improvements on decision-to-delivery interval (DDI) in case of emergency cesarean sections. METHODS: A retrospective observational Before-After study conducted in a type III maternity, first from 2004 to 2009 (Period 1, P1) then after moving our unit to new premises from 2009 to 2013 (P2). DDI, maternal and neonatal outcomes of every emergency cesarean section were studied. RESULTS: The mean DDI of extremely urgent cesarean significantly decreased from 21...
October 27, 2017: Gynecologie, Obstetrique, Fertilite & Senologie
https://www.readbyqxmd.com/read/29109936/a-study-of-harmful-drug-drug-interactions-due-to-polypharmacy-in-hospitalized-patients-in-goa-medical-college
#10
Akshay Khandeparkar, Padmanabh V Rataboli
Introduction: Concomitant use of multiple drugs is often indicated to manage comorbid conditions and enhance efficacy. Such concomitant use of multiple drugs (five or more drugs) has been defined as "polypharmacy." Polypharmacy has been associated with adverse consequences such as greater healthcare costs, increased risk of adverse drug events, drug-drug interactions (DDIs), medication nonadherence, reduced functional capacity, and multiple geriatric syndromes. This study evaluated number of potential harmful DDIs due to polypharmacy...
October 2017: Perspectives in Clinical Research
https://www.readbyqxmd.com/read/29105703/-disturbo-dissociativo-d-identit%C3%A3-auto-ipnosi-e-sintomi-simil-psicotici-da-un-caso-clinico-a-un-problema-di-diagnosi-differenziale
#11
Corinna Pancheri, Maria Caredda, Isabella Pacchiarotti, Roberto Delle Chiaie, Massimo Biondi
RIASSUNTO. Presentiamo il caso clinico di un paziente di 49 anni al suo esordio psicopatologico. La presenza di un'alterazione del tono dell'umore con sintomi schneideriani di primo rango nel contesto di un chiaro stato dissociativo simile alla trance ipnotica potrebbe portare, in un primo momento, a una diagnosi di disturbo bipolare avviando così il paziente verso un preciso iter terapeutico. Tuttavia riteniamo che la presenza di importanti segni di dissociazione associati alla pratica incontrollata dell'auto-ipnosi e alla presenza di "voci interne" in un paziente fortemente predisposto alla dissociazione permetta di porre una diagnosi sovraordinata di disturbo dissociativo di identità (DDI)...
September 2017: Rivista di Psichiatria
https://www.readbyqxmd.com/read/29102550/a-physiologically-based-pharmacokinetic-modeling-approach-to-predict-drug-drug-interactions-of-buprenorphine-after-subcutaneous-administration-of-cam2038-with-perpetrators-of-cyp3a4
#12
Tao Liu, Jogarao V S Gobburu
CAM2038, FluidCrystral (FC) injection depot, is an extended release formulation of buprenorphine given subcutaneously every 1 week (Q1W) or every 4 weeks (Q4W). The purpose of this research is to predict the magnitude of drug-drug interaction (DDI) after coadministration of a strong CYP3A4 inducer or inhibitor using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model was developed for CAM2038 based on the previously published buprenorphine PBPK model after intravenous (IV) and sublingual (SL) administration and the PK profiles after SC administration of CAM2038 from two Phase I clinical trials...
November 1, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29098941/efflux-transporter-breast-cancer-resistance-protein-dominantly-expresses-on-the-membrane-of-red-blood-cells-hinders-partitioning-of-its-substrates-into-the-cells-and-alters-drug-drug-interaction-profiles
#13
Pu Shi, Mingxiang Liao, Bei-Ching Chuang, Robert Griffin, Judy Shi, Marc Hyer, John K Fallon, Philip C Smith, Chao Li, Cindy Q Xia
1. Red blood cell (RBC) partitioning is important in determining pharmacokinetic and pharmacodynamic properties of a compound; however, active transport across RBC membranes is not well understood, particularly without transporter-related cell membrane proteomics data. 2. In this study, we quantified breast cancer resistance protein (BCRP/Bcrp) and MDR1/P-glycoprotein (P-gp) protein expression in RBCs from humans, monkeys, dogs, rats, and mice using nanoLC/MS/MS, and evaluated their effect on RBC partitioning and plasma exposure of their substrates...
November 3, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29079968/prediction-of-drug-drug-interaction-potential-using-physiologically-based-pharmacokinetic-modeling
#14
REVIEW
Jee Sun Min, Soo Kyung Bae
The occurrence of drug-drug interactions (DDIs) can significantly affect the safety of a patient, and thus assessing DDI risk is important. Recently, physiologically based pharmacokinetic (PBPK) modeling has been increasingly used to predict DDI potential. Here, we present a PBPK modeling concept and strategy. We also surveyed PBPK-related articles about the prediction of DDI potential in humans published up to October 10, 2017. We identified 107 articles, including 105 drugs that fit our criteria, with a gradual increase in the number of articles per year...
October 27, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29077847/drug-drug-interaction-extraction-via-hierarchical-rnns-on-sequence-and-shortest-dependency-paths
#15
Yijia Zhang, Wei Zheng, Hongfei Lin, Jian Wang, Zhihao Yang, Michel Dumontier
Motivation: Adverse events resulting from drug-drug interactions (DDI) pose a serious health issue. The ability to automatically extract DDIs described in the biomedical literature could further efforts for ongoing pharmacovigilance. Most of neural networks-based methods typically focus on sentence sequence to identify these DDIs, however the shortest dependency path (SDP) between the two entities contains valuable syntactic and semantic information. Effectively exploiting such information may improve DDI extraction...
October 25, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29063553/contributions-from-the-2016-literature-on-clinical-decision-support
#16
V Koutkias, J Bouaud
Objectives: To summarize recent research and select the best papers published in 2016 in the field of computerized clinical decision support for the Decision Support section of the IMIA yearbook. Methods: A literature review was performed by searching two bibliographic databases for papers related to clinical decision support systems (CDSSs). The aim was to identify a list of candidate best papers from the retrieved papers that were then peer-reviewed by external reviewers. A consensus meeting of the IMIA editorial team finally selected the best papers on the basis of all reviews and section editor evaluation...
August 2017: Yearbook of Medical Informatics
https://www.readbyqxmd.com/read/29058038/drug-drug-interactions-and-their-harmful-effects-in-hospitalised-patients-a-systematic-review-and-meta-analysis
#17
REVIEW
Wu Yi Zheng, L C Richardson, L Li, R O Day, J I Westbrook, M T Baysari
PURPOSE: Drug-drug interactions (DDIs) are often avoidable and, if undetected, can lead to patient harm. This review aimed to determine the prevalence of potential DDIs (pDDIs), clinically relevant DDIs (DDIs that could lead to measurable patient harm, taking into account the patient's individual clinical profile) and DDIs that resulted in actual patient harm during hospitalisation. METHOD: Four databases were scanned for English papers published from 2000 to 2016...
October 23, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29052226/translational-high-dimensional-drug-interaction-discovery-and-validation-using-health-record-databases-and-pharmacokinetics-models
#18
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/29034375/extracting-drug-drug-interactions-with-word-and-character-level-recurrent-neural-networks
#19
Ramakanth Kavuluru, Anthony Rios, Tung Tran
Drug-drug interactions (DDIs) are known to be responsible for nearly a third of all adverse drug reactions. Hence several current efforts focus on extracting signal from EMRs to prioritize DDIs that need further exploration. To this end, being able to extract explicit mentions of DDIs in free text narratives is an important task. In this paper, we explore recurrent neural network (RNN) architectures to detect and classify DDIs from unstructured text using the DDIExtraction dataset from the SemEval 2013 (task 9) shared task...
August 2017: IEEE International Conference on Healthcare Informatics IEEE International Conference on Healthcare Informatics
https://www.readbyqxmd.com/read/29017459/an-attention-based-effective-neural-model-for-drug-drug-interactions-extraction
#20
Wei Zheng, Hongfei Lin, Ling Luo, Zhehuan Zhao, Zhengguang Li, Yijia Zhang, Zhihao Yang, Jian Wang
BACKGROUND: Drug-drug interactions (DDIs) often bring unexpected side effects. The clinical recognition of DDIs is a crucial issue for both patient safety and healthcare cost control. However, although text-mining-based systems explore various methods to classify DDIs, the classification performance with regard to DDIs in long and complex sentences is still unsatisfactory. METHODS: In this study, we propose an effective model that classifies DDIs from the literature by combining an attention mechanism and a recurrent neural network with long short-term memory (LSTM) units...
October 10, 2017: BMC Bioinformatics
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