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Current Drug Metabolism

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https://www.readbyqxmd.com/read/28524006/circulating-tumor-cells-a-reliable-biomarker-for-prostate-cancer-treatment-assessment
#1
Chiara Ciccarese, Rodolfo Montironi, Michelangelo Fiorentino, Guido Martignoni, Matteo Brunelli, Roberto Iacovelli, Antonio Lopez-Beltran, Liang Cheng, Marina Scarpelli, Holger Moch, Giampaolo Tortora, Francesco Massari
Prostate cancer is a common malignancy with highly molecular heterogeneity responsible for a wide spectrum of clinical behavior. To date, several treatment options are available, whose selection is currently based mainly on clinical criteria. Given the weakness of conventional imaging and PSA assay, the identification of a prognostic and predictive biomarker for choosing the appropriate treatment and monitoring its efficacy is a very topical issue in prostate cancer management. Circulating tumor cells (CTCs) have substantial promise for early tumor diagnosis, disease recurrence and metastatic spread monitoring as well as for biological tumor characterization, thus representing a reliable translational real-time biomarkers of prostate cancer...
May 18, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28524005/rivaroxaban-metabolism-pharmacologic-properties-and-drug-interactions
#2
Tomas Kvasnicka, Ivana Malikova, Zuzana Zenahlikova, Karolína Kettnerova, Radka Brzezkova, Tomas Zima, Jan Ulrych, Jan Briza, Ivan Netuka, Jan Kvasnicka
BACKGROUND: Rivaroxaban represents a selective direct inhibitor of activated coagulation factor X (FXa) having peroral bioavailability and prompt onset of action. OBJECTIVE: The absorbtion of rivaroxaban is quick, reaching maximum plasma concentration 2-4 hours following its administration. Peroral bioavailability is high (80-100 %) and pharmacokinetic variability is considered to be moderate (coefficient of variation 30-40 %). This review discusses the properties, drug interactions, pharmacokinetics and clinical indications of rivaroxaban...
May 18, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28524004/urinary-biomarkers-for-prostate-cancer
#3
Francesca Giunchi, Chiara Ciccarese, Rodolfo Montironi, Marina Scarpelli, Antonio Lopez-Beltran, Liang Cheng, Holger Moch, Francesco Massari, Michelangelo Fiorentino
Urine may represent a convenient source of biomarkers for the early detection of prostate cancer (PCa) since contains secreted prostatic products and exfoliated tumor cells. Furthermore urine are easy to collect with non-invasive procedures and they are repeatable. Several urinary biomarkers for PCa have been proposed in the past but only one (PCA3) has been approved for clinical use and even this is not widely utilized in the routine practice. Most of these, particularly the proteins, were abandoned due to lack of confirmation...
May 18, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28524003/targeting-the-programmed-cell-death-1-pathway-in-genitourinary-tumors-current-progress-and-future-perspectives
#4
Rodolfo Montironi, Liang Cheng, Holger Moch, Antonio Lopez-Beltran, Marina Scarpelli, Francesco Massari, Michelangelo Fiorentino, Chiara Ciccarese, Michael Koch, Hristos Z Kaimakliotis, Lisha Wang, Roberto Pili, Steven A Mann
Immune checkpoint inhibitors have revolutionized the treatment many malignancies with over a dozen new United States Food and Drug Administration (FDA) approvals in the past six years. Due to the combination of potent treatment success and potentially deadly adverse effects from immune checkpoint inhibitors, gathering prognostic and predictive information about FDA-indicated tumors is prudent. PD-L1 expression is a poor prognostic factor and predictive of better responses from both PD-1 and PD-L1 inhibitors in a variety of tumor types including RCC and urothelial carcinoma...
May 18, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28524002/mirna-expression-in-bladder-cancer-and-their-potential-role-in-clinical-practice
#5
Ana Blanca, Liang Cheng, Rodolfo Montironi, Holger Moch, Francesco Massari, Michelangelo Fiorentino, Maria Rosaria Raspollini, Marina Scarpelli, Antonio Lopez-Beltran
To date more than 3000 miRNA sequences have been described in humans and reg¬istered at miRBase since their discovery. However, the functions of only a few of these miRNAs have been experimentally determined using deep sequencing technology. Aberrant miRNA expression has been associated with differentiation, invasion and metastasis in several cancers. In this context, recent reports have suggested that miRNAs play important roles in the regulation of target genes by binding to complementary regions of messenger transcripts to repress their translation or regulate degradation...
May 18, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28472910/helix-coil-transition-signatures-braf-v600e-mutation-and-virtual-screening-for-inhibitors-directed-against-mutant-braf
#6
Srinivas Bandaru, Tharaparambil Gangadharan Sumithnath, Saphy Sharda, Sanskruti Lakhotia, Anudeep Sharma, Amrita Jain, Tajamul Hussain, Anuraj Nayarisseri, Sanjeev Kumar Singh
Mutation in the B RAF at V600E has been well implicated in the carcinogenesis that makes it as an attractive therapeutic target. In the present study, we sought to identify the basis of V600E mutation at functional and structural grounds. The study also pursues to identify a candidate molecule with better pharmacological profiles than existing BRAF inhibitors through computational approaches. The functional effects of V600E mutation was predicted using SIFT and Polyphen servers. Protein structural alterations were predicted using SDM server and RMSD calculations...
May 2, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28460624/dabigatran-metabolism-pharmacologic-properties-and-drug-interactions
#7
Nebojsa Antonijevic, Ivana Zivkovic, Ljubica Jovanovic, Dragan Matic, Mladen Kocica, Igor Mrdovic, Vladimir Kanjuh, Milica Culafic
The superiority of dabigatran has been well proven in the standard dosing regimen in prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and extended venous thromboembolism (VTE) treatment. Dabigatran, an anticoagulant with a good safety profile, reduces intracranial bleeding in patients with atrial fibrillation and decreases major and clinically relevant non-major bleeding in acute VTE treatment. However, several important clinical issues are not fully covered by currently available directions with regard to dabigatran administration...
April 26, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28460623/vitamin-d-metabolism-and-potential-effects-of-vitamin-d-receptor-modulation-in-chronic-kidney-disease
#8
Antonio Bellasi, Andrea Galassi, Michela Mangano, Luca Di Lullo, Mario Cozzolino
Vitamin D deficiency is one determinant of secondary hyperparathyroidism in the course of Chronic Kidney Disease (CKD). However, numerous studies support the notion that vitamin D may exert pleiotropic effects aside of mineral metabolism control. Indeed, vitamin D receptor has been identified in a great variety of tissues and its activation contributes to the parathyroid, intestine, cardiovascular and immune system regulation. We herein review vitamin D metabolism and effects with a specific emphasis on the potential impact of vitamin D receptor modulation aside from parathyroid hormone control...
April 26, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28460622/intravesical-chemotherapy-and-chemohypherthermia-in-non-muscle-invasive-bladder-cancer-an-overview-on-drug-administration-technologies-and-pharmacokinetics
#9
Fabio Campodonico, Savino Di Stasi, Gad M Lev, Carlo Terrone, Luca Bongiovanni, Francesca Mattioli, Vincenzo Pagliarulo, Carlo Introini
BACKGROUND: Tumor recurrence is the most expected clinical event after the resection of non-muscle invasive bladder cancer, depending on histological findings of the initial lesion. In patients with low and intermediate risk of disease, the intravesical instillation of chemotherapy agents is recommended as a standard treatment to reduce recurrences. METHODS: A comprehensive review covering various aspects of different treatments with intravesical drugs is presented...
April 26, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28440204/apixaban-metabolism-pharmacologic-properties-and-drug-interaction
#10
Peter Kubisz, Lucia Stanciakova, Miroslava Dobrotova, Matej Samos, Marian Mokan, Jan Stasko
BACKGROUND: Apixaban is an oral, potent, highly selective, reversible and direct inhibitor of activated coagulation factor X, that is the end point of the intrinsic and extrinsic coagulation pathway. Additionally, apixaban has the capacity to indirectly inhibit thrombin-induced platelet aggregation. This new oral anticoagulant represents an immediate-release form of peroral drug with quick dissolution, linear pharmacokinetics, good bioavailability and rapid onset and offset of action...
April 24, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28413976/laboratory-monitoring-or-measurement-of-direct-oral-anticoagulants-doacs-advantages-limitations-and-future-challenges
#11
Emmanuel J Favaloro, Leonardo Pasalic, Jennifer Curnow, Giuseppe Lippi
BACKGROUND: The Direct Oral Anticoagulants (DOACs) represent a new generation of antithrombotic agents, providing direct inhibition of either thrombin (factor IIa; FIIa) or activated factor X (FXa). Around the globe, their use is progressively rising, as these new agents replace the historical anticoagulants (heparin and vitamin K antagonists including warfarin) for various clinical conditions in medical practice. Other acronyms used to designate DOACs include TSOAC (target specific oral anticoagulants) and NOAC (novel; or non-vitamin K antagonist oral anticoagulants)...
April 17, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28412908/news-in-the-indications-of-non-vitamin-k-oral-anticoagulants-according-to-the-guidelines-of-the-american-college-of-chest-physicians-2016
#12
Gabriela Cesarman-Maus, Guillermo J. Ruiz-Argüelles
Antithrombotic guidelines published by the Chest Journal, the official publication of the American College of Chest Physicians (ACCP), are continuously updated as clinically relevant information accumulates. The Evidence-Based Clinical Practice Guidelines on antithrombotic therapy and prevention of thrombosis were published in 2012. This year, the topic that has been updated pertains to antithrombotic therapy, specifically addressing prophylaxis and treatment of venous thromboembolic (VTE) disease. In this paper, I focus on these guidelines regarding the indications or lack thereof for the use of Non-vitamin K-antagonist Oral Anticoagulants (NOACS), also referred to as Direct-acting Oral Anticoagulants (DOACS)...
April 13, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28412907/review-of-the-pharmacology-of-the-emerging-possibilities-of-the-direct-oral-anticoagulants-reversal
#13
Matej Samos, Lucia Stanciakova, Ingrid Skornova, Tomas Bolek, Frantisek Kovar, Jan Stasko, Peter Galajda, Marian Mokan, Peter Kubisz
BACKGROUND: Direct oral anticoagulants (DOACs) offer consistent and predictable anticoagulation, oral administration with good patient compliance and a good safety profile. Dabigatran - a direct thrombin inhibitor, apixaban and rivaroxaban - direct factor Xa inhibitors are now largely used for anticoagulation in patients with non-valvular atrial fibrillation and in patients with venous thromboembolism. These agents have emerged as an expediential clinical choice in long-term anticoagulation for an increasing number of patients...
April 13, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28382862/inflammatory-bowel-disease-new-therapeutic-options-in-the-post-anti-tnf%C3%AE-era
#14
Miguel Jiménez Pérez, Raúl V Olmedo Martín, Víctor M Amo Trillo, Rocío González Gande
Inflammatory bowel diseasesare chronic bowel disorders the causes of which have not been fully elucidated,though they all sharean immunological basis. They have an important impact on both quality of life of the patient and on healthcare services. The incorporation of biological agents against tumour necrosis factor (TNF) alpha some 15 years ago represented a revolution in the management of patients with disease that did not respond to conventional treatment, enabling an overall improvement in the quality of life of many of these patients...
April 6, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28382861/metabolism-of-drugs-used-in-the-therapy-of-seizures-an-analytical-point-of-view-part-1
#15
Roberto Mandrioli, Laura Mercolini
BACKGROUND: Seizures are aetiologically and clinically heterogeneous neurological disorders that are currently treated using a wide array of drugs, belonging to equally heterogeneous chemical classes. Some of them are known as "antiepileptic drugs" (AEDs), due to their main field of use, while others (such as benzodiazepines) are frequently used for other conditions as well as for seizures. Due to their different chemical properties and mechanisms of activity, the metabolic characteristics of anti-seizure drugs can vary widely, also producing big differences in terms of safety, efficacy and therapeutic suitability...
April 6, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28322159/towards-predicting-the-cytochrome-p450-modulation-from-qsar-to-proteochemometric-modeling
#16
Watshara Shoombuatong, Philip Prathipati, Veda Prachayasittikul, Nalini Schaduangrat, Aijaz Ahmad Malik, Reny Pratiwi, Sompon Wanwimolruk, Jarl E S Wikberg, Matthew Paul Gleeson, Ola Spjuth, Chanin Nantasenamat
Drug metabolism determines the fate of a drug when it enters the human body and is a critical factor in defining their absorption, distribution, metabolism, excretion and toxicity (ADMET) characteristics. Among the various drug metabolizing enzymes, cytochrome P450s (CYP450) constitute an important protein family that aside from functioning in xenobiotic metabolism is also responsible for a diverse array of other roles encompassing steroid and cholesterol biosynthesis, fatty acid metabolism, calcium homeostasis, neuroendocrine functions and growth regulation...
March 20, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28302029/in-silico-adme-studies-for-new-drug-discovery-from-chemical-compounds-to-chinese-herbal-medicines
#17
Guojun Yan, Xiaobing Wang, Zhou Chen, Xianhui Wu, Jinhuo Pan, Yushen Huang, Gang Wan, Zhaogang Yang
Nowadays, in-silico tools are widely used to provide the potential structure of the metabolites formed depending on the site of metabolism. These methods can also highlight the molecular moieties that help to direct the molecule into the cytochrome cavity so that the site of metabolism is in proximity to the catalytic center. In this mini-review, we summarized three aspects of the in-silico methods in the application of prediction the ADME (absorption, distribution, metabolism and excretion) properties of compounds: structure-based approaches for predicting molecular modeling of drug metabolizing enzymes; in-silico metabolite prediction; and pharmacophore models for analysis substrate specificity...
March 15, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28302028/quantum-mechanical-qm-calculations-applied-to-admet-drug-prediction-a-review
#18
Edeildo F Silva-Júnior, J X Araújo-Júnior, T M Aquino
The discovery of new drugs is generally considered a long and expensive process, which often leads to molecules with low efficacy and high toxicity, which in many cases can be related to metabolism. In an attempt to reduce these failures and the production costs of a new drug, in silico studies have been used to obtain important information about the behavior of these compounds in the metabolism phases: absorption, distribution, metabolism (or biotransformation) and elimination (or excretion). Quantum Mechanical (QM) calculations are based on Schrödinger's equation can be used to develop models and theoretical parameters able to explain properties observed experimentally...
March 15, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28302027/in-silico-design-and-admet-studies-of-natural-compounds-as-inhibitors-of-xanthine-oxidase-xo-enzyme
#19
Neelam Malik, Priyanka Dhiman, Anurag Khatkar
BACKGROUND: Xanthine oxidase a ubiquitous enzyme has been found to be involved in various pathological disorders including gout, hyperuricemia, inflammation, oxidative stress and cardiovascular diseases. Inhibitors of xanthine oxidase thus find a crucial role in the therapeutic treatment of these deadly diseases. OBJECTIVE: Considering the side effects of today's treatment regimen here we choose nature based compounds to act as xanthine oxidase inhibitors. In the present work, we performed in-silico docking of natural compounds to reveal the underlying mechanism of inhibition of xanthine oxidase...
March 15, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28302026/drug-metabolism-in-preclinical-drug-development-a-survey-of-the-discovery-process-toxicology-and-computational-tools
#20
Naiem T Issa, Henri Wathieu, Abiola Ojo, Stephen W Byers, Sivanesan Dakshanamurthy
Increased R & D spending and high failure rates exist in drug development, due in part to inadequate prediction of drug metabolism and its consequences in the human body. Hence, there is a need for computational methods to supplement and complement current biological assessment strategies. In this review, we provide an overview of drug metabolism in pharmacology, and discuss the current in vitro and in vivo strategies for assessing drug metabolism in preclinical drug development. We highlight computational tools available to the scientific community for the in silico prediction of drug metabolism, and examine how these tools have been implemented to produce drug-target signatures relevant to metabolic routes...
March 15, 2017: Current Drug Metabolism
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