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Current Drug Metabolism

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https://www.readbyqxmd.com/read/28595534/a-review-of-levetiracetam-in-neonates
#1
Amit Agrawal, Anita Banergee
BACKGROUND: Neonatal seizures are the most common clinical manifestation of central nervous system (CNS) dysfunction and are associated with various neurological sequelae. There are currently no evidence-based guidelines for the management of neonatal seizures and currently used drugs such as phenobarbital, and phenytoin have limited efficacy and potential toxicities. Newer second line anticonvulsant, levetiracetam, has been used in refractory neonatal seizures despite limited data and off-label use...
June 6, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28595533/recent-advances-of-computational-modeling-for-predicting-drug-metabolism-a-perspective
#2
Supratik Kar, Jerzy Leszczynski
Absorption, Distribution, Metabolism, Excretion (ADME) properties along with drug induced adverse effects are the major reasons for the late stage failure of drug candidates as well as cause for the expensive withdrawal of many approved drugs from the market. Considering adverse effects of drugs, metabolism factor has great importance in medicinal chemistry and clinical pharmacology because it influences the deactivation, activation, detoxification and toxification of drugs. Computational methods are effective approaches to reduce the number of safety issues by analyzing possible links between chemical structures and metabolism followed by adverse effects, as they serve the integration of information on several levels to enhance the reliability of outcomes...
June 6, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28595532/pharmacological-and-toxicological-profile-of-harmane-%C3%AE-carboline-alkaloid-friend-or-foe
#3
Haroon Khan, Seema Patel, Mohammad A Kamal
The plant secondary metabolites have an outstanding therapeutic potential and success over the years. In fact, it is the foundation of numerous clinically used drugs. Similarly, there is a general perception that these products usually have safe option. However, such products might have toxic/unwanted lethal effects therefore, along with biological relevance, toxicological evaluation is equally important for clinical applications. Harmane-β-carboline alkaloid has shown several pharmacological activities such as antianxiety, antidepressant, antiplatelet, antidiabetic, acetylcholinesterase and myeloperoxidase inhibition, antioxidant, antiparasitic, hypotensive, morphine withdrawal syndrome alleviation, and antinociceptive effects...
June 6, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28595531/repurposed-drugs-as-potential-therapeutic-candidates-for-management-of-alzheimer-s-disease
#4
Muhammad Shoaib, Mohammad A Kamal, Syed Mohd Danish Rizvi
Drug repurposing is an innovative approach as it provides fresh implications to previously approved and established drug compounds. Due to high failure rates and cost involved in the drug development process, many pharmaceutical companies are primarily focusing on drug repurposing strategy. In Alzheimer disease, existing therapeutic agents only provide symptomatic benefits and does not get involved in disease modification, therefore, the alternative approach of repurposing could be applied to inhibit neurodegeneracy process and other pathological complications...
June 6, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28558634/differential-regulation-of-cyp3a4-and-cyp3a5-and-its-implication-in-drug-discovery
#5
Ogheneochukome Lolodi, Yue-Ming Wang, William C Wright, Taosheng Chen
Cancer cells use several mechanisms to resist the cytotoxic effects of drugs, resulting in tumor progression and invasion. One such mechanism capitalizes on the body's natural defense against xenobiotics. Recent reports indicate that components of the xenobiotic response system are upregulated in some diseases, including many cancers. Such components include the pregnane X receptor and the cytochrome P450 3A4 and 3A5 enzymes. Intense research is ongoing to understand the functional ramifications of aberrant expression of these components in diseased states with the goal of designing novel drugs that can selectively target them...
May 30, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28558633/impact-of-drug-metabolism-pharmacokinetics-and-their-relevance-upon-salvia-based-drug-discovery
#6
Da-Cheng Hao, Pei-Gen Xiao
Salvia is the largest genus of family Lamiaceae and has nearly 1000 species. This genus produces several representative phytometabolites, e.g., diterpenoids and phenolic acids. The traditional uses in ethnomedicine and contemporary experimental studies have corroborated extensive therapeutic efficacy of Salvia plants. Drug metabolism and pharmacokinetic (DMPK) studies of Salvia natural products and their derivatives are indispensable in the optimization of lead compounds. New chemical entity with improved DMPK profiles is preferred...
May 30, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28524006/circulating-tumor-cells-a-reliable-biomarker-for-prostate-cancer-treatment-assessment
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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