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Expert Opinion on Drug Metabolism & Toxicology

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https://www.readbyqxmd.com/read/28511565/the-role-of-membrane-transporters-in-ovarian-cancer-chemoresistance-and-prognosis
#1
Ela Cerovska, Katerina Elsnerova, Radka Vaclavikova, Pavel Soucek
Ovarian cancer has the highest mortality rate of all cancers in women. There is currently no effective method for early diagnosis, limiting the precision of clinical expectations. Predictions of therapeutic efficacy are currently not available either. Specifically, the development of chemoresistance against conventional chemotherapy poses a fundamental complication. Some membrane transporters have been reported to influence chemoresistance, which is often associated with a poor prognosis. Areas covered: The aim of this article is to review the existing information about membrane transporters and their role in both ovarian cancer chemoresistance and its outcomes...
May 16, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28490206/pharmacokinetics-pharmacodynamics-and-pharmacogenetics-associated-with-nonsteroidal-anti-inflammatory-drugs-and-opioids-in-pediatric-cancer-patients
#2
Jonathan Constance, Sarah Campbell, Amit A Somani, Venkata Yellepeddi, Katie Owens, Catherine Sherwin
Advancing appropriate and adequate analgesic pharmacotherapy in pediatric patients with cancer is an area of clinical need. Few studies have been performed to evaluate the selection of an analgesic and appropriate dosing corresponding to analgesic effect among pediatric cancer patients. This review describes information related to pharmacokinetic, pharmacodynamic, and pharmacogenomic (when applicable) considerations for analgesics that are commonly used to manage pain experienced by pediatric patients with cancer...
May 11, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28460576/pharmacokinetic-and-pharmacodynamic-alterations-in-older-people-with-dementia
#3
Emily Reeve, Shanna C Trenaman, Kenneth Rockwood, Sarah N Hilmer
The number of people with dementia internationally is increasing. Older adults with dementia are prescribed multiple medications, both to treat dementia symptoms and to manage their other medical conditions. Dementia is correlated with increasing age and frailty; this provides insight into how the efficacy and toxicity of medications may be altered in people with dementia. Areas covered: This review discusses the current evidence of the alterations in pharmacokinetics that can occur with aging, frailty and in people with dementia...
May 10, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28486001/predicting-and-preventing-antimicrobial-resistance-utilizing-pharmacodynamics-part-ii-gram-negative-bacteria
#4
Kamilia Abdelraouf, Kristin E Linder, Michael D Nailor, David P Nicolau
INTRODUCTION: Antimicrobial resistance is a serious health threat worldwide. Better understanding of exposure targets that could suppress resistance amplification is necessary to guide the dosing of currently available agents as well as new therapies in the drug development process. AREAS COVERED: This review will discuss studies that focused on predicting development of resistance using the pharmacokinetic-pharmacodynamic approach and how to design dosing regimens that can successfully suppress resistance emergence in Gram-negative bacteria...
May 9, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28460549/pharmacokinetic-drug-evaluation-of-brodalumab-for-the-treatment-of-psoriasis
#5
M Galluzzo, M Talamonti, S D'adamio, L Bianchi
Psoriasis is now understood to also be under the driving influence of the IL-17/IL-23 axis, and the medical breakthrough of novel IL-17 inhibitor medications signals a paradigm shift in the way psoriatic patients are managed medically. Brodalumab, a fully human Chinese hamster ovary cell-derived immunoglobulin G2 (IgG2) anti-IL-17RA monoclonal antibody, is currently the most-developed treatment that binds to the IL-17RA. The authors review and provide updates of efficacy and safety by several studies on brodalumab...
May 9, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28425772/prediction-of-successful-dose-reduction-or-discontinuation-of-adalimumab-etanercept-or-infliximab-in-rheumatoid-arthritis-patients-using-serum-drug-levels-and-antidrug-antibody-measurement
#6
Cam Bouman, N van Herwaarden, Fhj van den Hoogen, A van der Maas, Bjf van den Bemt, A A den Broeder
BACKGROUND: To evaluate if TNF inhibitor serum drug levels (DL) or anti-drug antibodies (ADAb) can predict successful dose reduction (in patients with high DL) or discontinuation (in patients with no/low DL or ADAb) in rheumatoid arthritis (RA) patients. RESEARCH DESIGN AND METHODS: RA patients that were using adalimumab (n = 42), etanercept (n = 76) or infliximab (n = 51) and were doing well, were tapered until discontinuation or flare (1-1.5 year follow up)...
April 24, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28375027/characterisation-of-data-resources-for-in-silico-modelling-benchmark-datasets-for-adme-properties
#7
K R Przybylak, J C Madden, E Covey-Crump, L Gibson, C Barber, M Patel, M T D Cronin
The cost of in vivo and in vitro screening of ADME properties of compounds has motivated efforts to develop a range of in silico models. At the heart of the development of any computational model are the data; high quality data are essential for developing robust and accurate models. The characteristics of a dataset, such as its availability, size, format and type of chemical identifiers used, influence the modelability of the data. Areas covered: This review explores the usefulness of publicly available ADME datasets for researchers to use in the development of predictive models...
April 23, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28359183/changes-in-drug-transport-and-metabolism-and-their-clinical-implications-in-non-alcoholic-fatty-liver-disease
#8
Christoph G Dietrich, Monika Rau, Daniel Jahn, Andreas Geier
The incidence of non-alcoholic fatty liver disease (NAFLD) is rising, especially in Western countries. Drug treatment in patients with NAFLD is common since it is linked to other conditions like diabetes, obesity, and cardiovascular disease. Consequently, changes in drug metabolism may have serious clinical implications. Areas covered: A literature search for studies in animal models or patients with obesity, fatty liver, non-alcoholic steatohepatitis (NASH) or NASH cirrhosis published before November 2016 was performed...
March 31, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28343423/management-of-precipitated-opiate-withdrawal-syndrome-induced-by-nalmefene-mistakenly-prescribed-in-opiate-dependent-patients-a-review-for-clinicians
#9
Nicolas Franchitto, Benedicte Jullian, Juliette Salles, Fanny Pelissier, Benjamin Rolland
Nalmefene, a long-acting µ-opioid antagonist approved to treat alcohol use disorder, is occasionally mistakenly prescribed to opiate-dependent or opioid-treated patients. We review recent literature on drug-drug interactions between nalmefene and opioids that lead to precipitated opioid withdrawal, and focus on its management and planning for care at discharge. Areas covered: This article provides a brief and comprehensive review of management of precipitated opioid withdrawal syndrome when nalmefene is associated with an opioid, whether misused or legally prescribed...
March 27, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28335648/inflammation-and-pharmacokinetics-potential-implications-for-hiv-infection
#10
Sharon M Seifert, Jose R Castillo-Mancilla, Kristine M Erlandson, Peter L Anderson
The physiological changes accompanying inflammation may alter the pharmacokinetics (PK) of certain medications. Individuals infected with HIV have chronically elevated inflammatory markers despite viral suppression following effective antiretroviral therapy (ART), as well as age-related inflammation. Understanding the potential clinical implications of inflammation on the PK of medications is important for understanding dose-response relationships and necessitates future research. Areas covered: An extensive literature search was carried out using PubMed and associated bibliographies to summarize the current state of knowledge regarding altered PK in response to inflammation and its application to the field of HIV...
March 24, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28274165/erratum
#11
(no author information available yet)
No abstract text is available yet for this article.
March 8, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28395543/pharmacokinetic-drug-evaluation-of-ribociclib-for-the-treatment-of-metastatic-hormone-positive-breast-cancer
#12
Giuseppe Curigliano, Carmen Criscitiello, Angela Esposito, Mattia Intra, Saverio Minucci
Cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4/6-retinoblastoma (Rb) pathway hyperactivation is associated with hormone receptor-positive (HR+) breast cancer (BC). Ribociclib is an orally bioavailable, highly selective small molecule inhibitor of CDK4/6 that induces G1 arrest at sub-micromolar concentrations in a variety of pRb-positive cancer cells in vitro. Ribociclib is a new standard of care for metastatic HR+/HER2 negative metastatic breast cancer. Area covered: In this article, we review the preclinical and clinical development of ribociclib as well as discussing the role for novel applications of these agents outside the arena of HR-positive, HER2-negative advanced breast cancer...
May 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28374622/pharmacokinetic-drug-evaluation-of-saxagliptin-plus-dapagliflozin-for-the-treatment-of-type-2-diabetes
#13
André J Scheen
Combining a dipeptidyl peptidase-4 inhibitor and a sodium-glucose cotransporter type 2 inhibitor is an attractive option to treat hyperglycaemia in type 2 diabetes. Areas covered: The saxagliptin plus dapagliflozin combination is carefully analysed, focusing on: 1) pharmacokinetic properties, 2) pharmacodynamics data, and 3) results of randomised controlled trials (dual combination versus either monotherapy, sequential therapy saxagliptin added to dapagliflozin or dapagliflozin added to saxagliptin). Expert opinion: Pharmacokinetic findings demonstrate the absence of drug-drug interaction and the bioequivalence of the FDC compared with separated tablets...
May 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28151695/pharmacokinetic-considerations-for-patients-with-a-history-of-bariatric-surgery
#14
Célia Lloret-Linares
No abstract text is available yet for this article.
May 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28150517/human-biology-based-drug-safety-evaluation-scientific-rationale-current-status-and-future-challenges
#15
J Gerry Kenna
Animal toxicity studies used to assess the safety of new candidate pharmaceuticals prior to their progression into human clinical trials are unable to assess the risk of non-pharmacologically mediated idiosyncratic adverse drug reactions (ADRs), the most frequent of which are drug-induced liver injury and cardiotoxicity. Idiosyncratic ADRs occur only infrequently and in certain susceptible humans, but are caused by many hundreds of different drugs and may lead to serious illness. Areas covered: Idiosyncratic ADRs are initiated by drug-related chemical insults, which cause toxicity due to susceptibility factors that manifest only in certain patients...
May 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28141945/drug-induced-renal-injury-in-neonates-challenges-in-clinical-practice-and-perspectives-in-drug-development
#16
Anna Girardi, Emanuel Raschi, Silvia Galletti, Karel Allegaert, Elisabetta Poluzzi, Fabrizio De Ponti
Acute kidney injury (AKI) is frequently diagnosed in the neonatal population, especially in those admitted to intensive care units, and poses several challenges for clinicians mainly because of difficulties in timely identification of renal impairment and the need to administer drugs with potential nephrotoxicity. In this context, research on biomarkers is growing for their implication in the early detection of renal damage and their higher sensitivity in monitoring renal activity, but also as an important tool for drug development...
May 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28043170/impact-of-disease-drug-and-patient-adherence-on-the-effectiveness-of-antiviral-therapy-in-pediatric-hiv
#17
Chiara Piana, Meindert Danhof, Oscar Della Pasqua
Maintaining effective antiretroviral treatment for life is a major problem in both resource-limited and resource-rich countries. Despite the progress observed in paediatric antiretroviral therapy, approximately 12% of children still experience treatment failure due to drug resistance, inadequate dosing and poor adherence. We explore the current status of antiretroviral therapy in children with focus on the interaction between disease, drug pharmacokinetics and patient behavior, all of which are strongly interconnected and determine treatment outcome...
May 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28019118/the-mechanisms-of-cyclophosphamide-induced-testicular-toxicity-and-the-protective-agents
#18
Emad Ghobadi, Milad Moloudizargari, Mohammad Hossein Asghari, Mohammad Abdollahi
Cyclophosphamide (CP) is an alkylating antineoplastic agent with known toxicity to the male reproductive system. Areas covered: This review summarizes the known mechanisms by which CP exerts its toxic effects on the male reproductive system and the methods utilized to prevent such effects so that it could be further investigated and applied in clinical use. Keywords including ['Cyclophosphamide' AND 'male reproductive' OR' sperm toxicity' OR 'spermatotoxicity' OR 'infertility] were searched through Google Scholar, PubMed and Scopus databases based on PRISMA guidelines...
May 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27936967/potential-roles-of-myeloperoxidase-and-hypochlorous-acid-in-metabolism-and-toxicity-of-alkene-hydrocarbons-and-drug-molecules-containing-olefinic-moieties
#19
Xin-Yu Zhang, Adnan A Elfarra
Adverse drug reactions (ADRs) pose a significant health problem and are generally attributed to reactive metabolites. Olefinic moieties in drugs can undergo cytochrome P450-mediated bioactivation to produce reactive metabolites but myeloperoxidase (MPO)-mediated bioactivation of these moieties has not been reported. Thus, small molecules of alkene hydrocarbons are used as model compounds to characterize the MPO-mediated metabolism. Areas covered: The authors focus on MPO-mediated metabolism of alkene hydrocarbons to form chlorohydrins and the potential role of chlorohydrins in alkene toxicity and carcinogenicity...
May 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27696906/the-role-of-fulvestrant-in-endometrial-cancer
#20
Stefano Bogliolo, Chiara Cassani, Mattia Dominoni, Anna Orlandini, Simone Ferrero, Anna Daniela Iacobone, Franco Viazzo, Pier Luigi Venturini, Arsenio Spinillo, Barbara Gardella
Endometrial cancer is the most common malignancy of the female genital tract in industrialized countries. The traditional treatment of endometrial cancer is based on a surgical approach. In recent years, systemic endocrine therapy has demonstrated good efficacy in recurrent or metastatic setting, delaying progression, ameliorating quality of life and palliating symptoms. Areas covered: Phase I and II studies on selective estrogen receptor down-regulators used for the treatment of endometrial cancer treatment have been reviewed...
May 2017: Expert Opinion on Drug Metabolism & Toxicology
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