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Expert Opinion on Drug Metabolism & Toxicology

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https://www.readbyqxmd.com/read/30277082/pharmacokinetics-of-new-oral-anticoagulants-implications-for-use-in-routine-care
#1
Ylenia Ingrasciotta, Salvatore Crisafulli, Valeria Pizzimenti, Ilaria Marcianò, Anna Mancuso, Giuseppe Andò, Salvatore Corrao, Piera Capranzano, Gianluca Trifirò
Since 2008, new oral anticoagulants (NOACs) have been approved for the prevention of venous thromboembolism (VTE) in patients receiving hip or knee replacement surgery, prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF), treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Pre-marketing randomized clinical trials of NOACs demonstrated their non-inferiority in terms of efficacy vs. warfarin (traditional oral anticoagulant - TOA), with lower risk of serious adverse drug reactions, especially cerebral haemorrhages...
October 2, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30269615/drug-pharmacomicrobiomics-and-toxicomicrobiomics-from-scattered-reports-to-systematic-studies-of-drug-microbiome-interactions
#2
Ramy K Aziz, Shaimaa M Hegazy, Reem Yasser, Mariam R Rizkallah, Marwa T ElRakaiby
Pharmacomicrobiomics and toxicomicrobiomics study how variations within the human microbiome (the combination of human-associated microbial communities and their genomes) affect drug disposition, action, and toxicity. These emerging fields, interconnecting microbiology, bioinformatics, systems pharmacology, and toxicology, complement pharmacogenomics and toxicogenomics, expanding the scope of precision medicine. Areas covered: This article reviews some of the most recently reported pharmacomicrobiomic and toxicomicrobiomic interactions...
October 1, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30265586/glucocorticoids-use-in-kidney-transplant-setting
#3
Débora Dias De Lucena, Érika Bevilaqua Rangel
INTRODUCTION: Despite major advances in kidney transplant, glucocorticoids (GCs) or steroids remain one of the mainstay treatments. They possess adverse events (AEs) that are related to cumulative dosage, as documented in experimental and clinical studies. Therefore, it is important to comprehend and interpret experimental data and equally important to critically review clinical studies. Areas covered: This article provides a broad overview of the structure, pharmacokinetics, and pharmacodynamics of systemically administered GCs in transplant setting...
September 28, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30261755/pharmacokinetic-considerations-concerning-the-use-of-bronchodilators-in-the-treatment-of-chronic-obstructive-pulmonary-disease
#4
Maria Gabriella Matera, Barbara Rinaldi, Clive Page, Paola Rogliani, Mario Cazzola
Bronchodilators are central to the symptomatic treatment of chronic obstructive pulmonary disease (COPD). Their pharmacodynamic aspects have been extensively described, but the pharmacokinetic profile of these drugs is much less well known. There are very few studies that describe the levels of drugs in the lung compartment following inhalation and to date very little is known about the relationships between drug levels in the lung and biological activity of bronchodilators. Areas covered: We review the evidence that exists on the pharmacokinetics of bronchodilators, especially when administered to patients with COPD...
September 28, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30251551/pharmacokinetics-and-drug-metabolism-of-antibiotics-in-the-elderly
#5
Federico Pea
The number of elderly people is increasing worldwide. The elderly may be at increased risk of bacterial infections in comparison with younger adults. Dosing adaptation of antibiotics in this population may be difficult due to changes in body composition, decline of renal function and/or drug-drug interactions. Lack of dose adaptation may cause unintentional overdosing with the risk of severe adverse effects. Areas covered: This review is based on a PubMed search of literature published in English language and concerns pharmacokinetic (PK) studies of antibiotics in the elderly performed between 1971 and 2017...
September 25, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30231780/correction
#6
(no author information available yet)
No abstract text is available yet for this article.
September 19, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30106599/pharmacokinetic-evaluation-of-meropenem-and-vaborbactam-for-the-treatment-of-urinary-tract-infection
#7
Rodrigo M Burgos, Mark J Biagi, Keith A Rodvold, Larry H Danziger
Meropenem/vaborbactam (M/V) represents the first carbapenem and β-lactamase inhibitor combination approved for treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a novel boronic acid, β-lactamase inhibitor with a high affinity for serine β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). This combination, Vabomere™, was approved in August 2017 by the United States Food and Drug Administration for the treatment of cUTIs in patients 18 years or older, including pyelonephritis, caused by the following susceptible microorganisms: Escherichia coli, K...
September 19, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30215280/drug-metabolism-and-metabolite-safety-assessment-in-drug-discovery-and-development
#8
Chunyong He, Hong Wan
Drug metabolism is one of the most important processes involving a drug after administration. Undesirable pharmacokinetic properties may lead to drug discontinuation. In the past several decades, a number of drugs have been withdrawn from the market due to safety issues caused by metabolites, especially reactive metabolites (RMs). Area covered: The focus of this review is on the role that drug metabolites play in drug discovery and developmental stages, with particular emphasis on metabolism-guided lead optimization, safety assessment of drug metabolites, drug-drug interaction potential of metabolites, and RMs safety assessment...
September 14, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30141352/pharmacokinetic-evaluation-of-the-aripiprazole-once-monthly-injection-for-the-treatment-of-bipolar-disorder
#9
Kaat Hebbrecht, Manuel Morrens, Hugo Neels, Laurence Roosens, Bernard G C Sabbe
Bipolar disorder is a severe, chronic psychiatric disorder with a need for long-term treatment. Patient nonadherence is frequent and poses a major problem in maintenance therapy. Aripiprazole once-monthly long-acting injectable (AOM LAI) is a recently US Food and Drug Administration-approved treatment option for maintenance therapy that could be of great value. Areas covered: This paper reviews the pharmacokinetic, efficacy and safety data for AOM LAI in bipolar disorder. Expert opinion: AOM LAI is a safe and efficacious treatment option in the maintenance therapy of bipolar I disorder...
September 7, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30134735/pharmacokinetics-of-tazarotene-and-acitretin-in-psoriasis
#10
REVIEW
Michael S Heath, Dev R Sahni, Zachary A Curry, Steven R Feldman
Psoriasis is a prevalent cutaneous condition with severe physical and psychological manifestations. Since the advent of biologics, clinical outcomes in psoriasis have improved. However, retinoids are useful in the correct clinical context. Tazarotene and acitretin are currently the only US Food and Drug Administration approved retinoids for treatment of psoriasis. Both topical tazarotene and oral acitretin act on retinoic acid receptors and retinoid-X-receptors, resulting in altered gene expression of inflammatory cytokines and inhibition of keratinocyte proliferation...
September 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30130984/pharmacokinetic-drug-evaluation-of-palbociclib-for-the-treatment-of-breast-cancer
#11
REVIEW
Antonella De Luca, Monica R Maiello, Amelia D'Alessio, Daniela Frezzetti, Marianna Gallo, Marianeve Carotenuto, Nicola Normanno
Cyclin-dependent kinases (CDKs) 4 and 6 regulate the transition from G0/G1-phase to S-phase of the cell cycle and have been identified as key drivers of proliferation in hormone receptor (HR)-positive breast cancer. The CDK4/6 inhibitor palbociclib in combination with endocrine therapy has been approved for treatment of HR-positive/HER2-negative breast cancer patients. Areas covered: In this article, we provide an update of the data on pharmacodynamics, pharmacokinetics, preclinical, and clinical studies of palbociclib in breast cancer...
September 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30118646/the-protective-role-of-melatonin-in-chemotherapy-induced-nephrotoxicity-a-review-of-non-clinical-studies
#12
REVIEW
Hamed Haghi-Aminjan, Bagher Farhood, Mahban Rahimifard, Tina Didari, Maryam Baeeri, Shokoufeh Hassani, Rohollah Hosseini, Mohammad Abdollahi
BSTRACT Introduction: The aim of this study was to investigate the potential role of melatonin in the prevention of chemotherapy-induced nephrotoxicity at the preclinical level. Areas to be covered: To illuminate the possible role of melatonin in preventing chemotherapy-related nephrotoxicity, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. A comprehensive search strategy was developed to include PubMed, Web of Science, Scopus, and Embase electronic databases from their inception to May 2018...
September 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30118608/impact-of-transporters-and-enzymes-from-blood-cerebrospinal-fluid-barrier-and-brain-parenchyma-on-cns-drug-uptake
#13
REVIEW
Qianwen Wang, Zhong Zuo
In parallel with the blood-brain barrier (BBB), transporters and enzymes on the blood-cerebrospinal fluid barrier (BCSFB) serve as the first barrier for drug brain uptake. In addition, their expressions on brain parenchyma are considered as the secondary barrier for central nervous system (CNS) drug delivery. Currently, a lack of information on transporters and enzymes expressed on both BCSFB and brain parenchyma is the major cause of failure in CNS drug development. Areas covered: Transporters and enzymes expressed on BCSFB and brain parenchyma and their impact on drug brain uptake were highlighted and compared with that on BBB...
September 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30099912/biomarkers-of-drug-induced-acute-kidney-injury-a-regulatory-perspective
#14
REVIEW
Melanie Blank, Aliza Thompson, Elizabeth Hausner, Rodney Rouse
Biomarkers are one of the drug development tools that are being developed through collaborative efforts among multiple stakeholder communities to enhance the drug development process. Biomarkers of acute drug-induced renal injury as used in drug development are more commonly referred to as renal safety biomarkers, the focus of this manuscript. Areas covered: This manuscript provides an overview of the history and evolution of the United States Food and Drug Administration's Center for Drug Evaluation and Research's Biomarker Qualification Program...
September 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30092669/characterization-of-drug-drug-interactions-in-patients-whose-substance-intake-was-objectively-identified-by-detection-in-urine
#15
Joshua Schrecker, Brandi Puet, Cheryl Hild, David M Schwope
BACKGROUND: Identification of drug-drug interactions (DDIs) typically relies on patient medication lists which are prone to inaccuracies. This study describes use of a mass spectrometry test to detect recently ingested substances in urine with subsequent identification of DDIs. RESEARCH DESIGN AND METHODS: This was a retrospective analysis of the prevalence of DDIs identified in patients with chronic pain, addiction and/or behavioral health conditions in the U.S...
September 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30074409/pharmacokinetic-and-pharmacodynamic-evaluation-of-ingenol-mebutate-for-the-treatment-of-actinic-keratosis
#16
REVIEW
Eggert Stockfleth, Mike Bastian
Actinic keratosis (AK) is a common skin condition that results from exposure to chronic ultraviolet (UV) radiation. AK is characterized by visible, scaly lesions; sub-clinical lesions may also be present within a field of UV-exposed skin. These lesions exist on a disease continuum with squamous cell carcinoma. Field therapies, such as ingenol mebutate, aim to treat the visible and sub-clinical lesions within an area of sun-damaged skin. Areas covered: According to the SmPC, ingenol mebutate has a proposed dual mechanism of action that induces cell death necrosis with the production of a local pro-inflammatory response and stimulation of apoptosis...
September 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30058394/pharmacodynamic-and-pharmacokinetic-evaluation-of-the-combination-of-daclatasvir-sofosbuvir-ribavirin-in-the-treatment-of-chronic-hepatitis-c
#17
REVIEW
Antonio Rivero-Juarez, Teresa Brieva, Mario Frias, Antonio Rivero
The combination of daclatasvir (DCV), sofosbuvir (SOF), and ribavirin (RBV) is a direct-acting antiviral (DAA) regimen for the treatment of hepatitis C virus (HCV) infection. The inclusion of newer effective DAAs such as SOF and DCV with high efficacy and excellent tolerance introduced a new scenario in HCV infection therapy: high rates of sustained virological response (SVR), shorter therapies, less toxicity, and interferon-free treatments. This combination was approved for the treatment of HCV in treatment-naive or treatment-experienced patients with chronic HCV genotype 1 or 3 infection...
September 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30058386/uterine-fibroid-therapy-the-pharmacokinetic-considerations
#18
Mohamed Ali, Ayman Al-Hendy
No abstract text is available yet for this article.
September 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30058385/improved-pharmacokinetic-characteristics-and-bioactive-effects-of-anticancer-enzyme-delivery-systems
#19
REVIEW
Shenglei Yan, Lan Yang, Luyang Lu, Qi Guo, Xueyuan Hu, Yuming Yuan, Yao Li, Mingjun Wu, Jingqing Zhang
Anticancer enzymes play important roles in cancer treatment. The anticancer enzyme has been in clinical use to treat acute lymphoblastic leukemia for many years. Other types of anticancer enzymes have been investigated in laboratory studies and clinical trials. Area covered: This paper will provide perspectives on the indications, anticancer mechanisms, enzymatic characteristics (such as molecular weight, organism source, and kinetic parameters) and pharmacokinetic behaviors of anticancer enzymes and their delivery systems by systematically analyzing available literature...
September 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/30049229/highly-selective-n-glucuronidation-of-four-piperazine-containing-drugs-by-udp-glucuronosyltransferase-2b10
#20
Danyi Lu, Dong Dong, Baojian Wu
BACKGROUND: N-glucuronidation is known to be an important metabolic pathway for detoxification and elimination of drugs containing aromatic amines. However, the metabolic pathways for piperazine-containing drugs are not fully established. METHODS: N-glucuronidation potential of four piperazine-containing drugs, namely two antihistamines (i.e. cyclizine and chlorcyclizine) and two tetracyclic antidepressants (i.e. mirtazapine and mianserin), was determined by using expressed UDP-glucuronosyltransferase (UGT) enzymes and liver microsomes from both human and animals...
September 2018: Expert Opinion on Drug Metabolism & Toxicology
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