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Current Drug Metabolism

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https://www.readbyqxmd.com/read/29962340/optimization-of-drugs-pharmacotherapy-during-pregnancy-using-physiologically-based-pharmacokinetic-models-an-update
#1
Nasir Idkaidek, Mo'tasem M Alsmadi
BACKGROUND: Clinical studies during pregnancy are rare due to ethical and practical limitations. Giving pregnant females the same dosing regimen used in adult males or nonpregnant females is inappropriate. Pregnancy physiologically-based pharmacokinetic modeling is a powerful tool that can be used to refine pharmacotherapy during pregnancy. OBJECTIVE: This work provides a review of the current status of application of physiologically based pharmacokinetic models in developing dosing regimens in pregnant women...
July 1, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29962339/thiazide-therapy-in-chronic-kidney-disease-renal-and-extra-renal-targets
#2
Negiin Pourafshar, Saeed Alshahrani, Ashkan Karimi, Manoocher Soleimani
Thiazides are the most commonly used medications for the treatment of mild and moderate hypertension. Despite their recognized effect, the mechanism by which thiazides reduce systemic blood pressure remains uncertain. The prevailing belief is that thiazides reduce blood pressure primarily via enhancement of salt excretion consequent to the inhibition of the Na-Cl cotransporter (NCC) in the distal convoluted tubules (DCT). However, recent reports point to a reduction in peripheral vascular resistance as a major mechanism of anti-hypertensive effect of thiazides...
July 1, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29956624/relevance-of-breast-cancer-resistance-protein-to-brain-distribution-and-central-acting-drugs-a-pharmacokinetic-perspective
#3
Joana Goncalves, Joana Bicker, Gilberto Alves, Ana Fortuna, Amilcar Falcao
BACKGROUND: Breast cancer resistance protein (BCRP, also known as ABCG2) is gaining momentum as a key transporter that restricts the permeability of a large number of therapeutic agents through the blood-brain barrier (BBB). BCRP is highly expressed in the apical membranes of epithelial cells of the small and large intestine, renal proximal tubules and canalicular membrane of hepatocytes, determining the gastrointestinal absorption and biodisposition of its substrates. It is also expressed in the luminal surface of endothelial cells of the BBB and blood-spinal cord barrier (BSCB), where it undoubtedly limits the entry of a wide range of therapeutics into the CNS, potentially contributing to the therapeutic failure of CNS-acting drugs...
June 29, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29956623/genetic-polymorphism-on-the-pharmacokinetics-and-pharmacodynamics-of-platelet-derived-growth-factor-receptor-pdgfr-kinase-inhibitors
#4
Yi Qian, Lei Yu, Xue-Hui Zhang, Qing-Yun Yuan-Zi, Ping Zhao, Lu-Ning Sun, Yong-Qing Wang
Platelet-derived Growth Factor Receptor (PDGFR) is one of the families of Receptor Tyrosine Kinases (RTKs), which have attracted increasing attention as a potential target of antitumor therapy in cancer. PDGFR family members consist of PDGFR-α, PDGFR-β, CSF-1R, KIT and FLT3. Tyrosine Kinase Inhibitors (TKIs) are a kind of small molecule inhibitors targeting RTKs. TKIs prevent and block vital pathways by targeting signaling molecules which are necessary for cell survival. At present, about 11 kinds of TKIs targeting PDGFR family members have been approved for the treatment of diseases like chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GIST), renal cell carcinoma (RCC), etc...
June 28, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29956622/pharmacological-and-therapeutic-potential-of-nitidine-a-plant-alkaloid
#5
Haroon Khan, Taibi Ben Hadda, Rachid Touzani, Mohammad A Kamal
Nitidine is a bioactive plant benzophenanthridine alkaloid isolated from the root of Zanthoxylum nitidum. Since its discovery in 1959, literature revealed marked anticancer, neuroprotective, antimalarial, anti-HIV, analgesic, anti-inflammatory, antifungal activities. MOE (molecular operating environment) ligand based pharmacophores features of nitidine showed that it has got multiple bioactive functional sites that implicating its sensitivity towards several receptors protein and therefore could be a useful lead compound...
June 28, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29956621/the-pharmacogenomics-of-asthma-beyond-its-endotypes
#6
Shuhui Meng, Shuyu Chen, Ailin Tao
Asthma is a heterogeneous disease that consists of different phenotypes and endotypes, driven by different mechanistic pathways. An increasing number of genetic loci and single-nucleotide polymorphisms have been associated with therapeutic responses to asthma drugs. The purpose of this review is to focus on certain susceptibility genes, gene variants and typical therapeutic drugs of the glucocorticoid, leukotriene, histamine, and β2-adrenergic receptor pathways related to asthma. Pharmacogenomics can help us better understand the genetic basis of drug responses and better define new therapeutic targets to improve treatment effectiveness...
June 28, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29956620/total-sleep-duration-and-risk-of-type-2-diabetes-evidence-based-on-clinical-and-epidemiological-studies
#7
Dhananjay Yadav, Kyung-Hyun Cho
Increasing incidences of type 2 diabetes makes it necessary to have a better understanding of the risk factors for its prediction. Taking a note of resilience in risk factors, dynamics of the emerging factors other than traditional ones are showing a great interest in recent years which imprints a significant contribution in the occurrence of diabetes. Of different factors, sleep duration was acknowledged as a most common risk factor for dyslipidemia, obesity, hypertension, metabolic syndrome and diabetes. Adhering to the state of information available, the review highlights the underlying mechanisms toward establishing the relationship between sleep duration and diabetes; compiled mainly through laboratory and epidemiological studies...
June 28, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29956619/current-designs-of-polymer-blends-in-solid-dispersions-for-improving-drug-bioavailability
#8
Phuong Ha-Lien Tran, Wei Duan, Beom-Jin Lee, Thao Td Tran
Ternary solid dispersions have been demonstrated to be an effective strategy in the improvement of drug absorption and bioavailability. The applications of the combination of hydrophilic polymers with the potential of hydrophobic polymer incorporation at moderate concentrations have been discussed in recent publications. In this paper, the general review of this specific type of solid dispersion will be provided with comprehensive understanding of polymer blends of either hydrophilic or hydrophobic polymers...
June 28, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29956618/metabolism-of-peptide-drugs-and-strategies-to-improve-their-metabolic-stability
#9
Jin-Feng Yao, Hong Yang, Yan-Zhi Zhao, Ming Xue
Peptides are used increasingly as therapeutics and biomarkers because of the development of peptide synthesis technologies. Although peptides are associated with a variety of advantages that include high pharmaceutical activity and low toxicity, the therapeutic use of peptides is limited because of their poor metabolic stability in vivo. The main cause of this instability is that peptides are readily degraded by peptidases distributed widely in the body. This review summarizes peptidases present in the gastrointestinal tract, blood, liver, kidney, nasal cavity and placental barrier, and provides an overview of the metabolic characteristics of peptides and recent strategies for improving the metabolic stability of peptide drugs...
June 28, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29938617/role-of-osmolytes-and-their-transporter-systems-in-pathogen-survival-and-pathogenicity
#10
Safikur Rahaman, Ayyagari Archana, Mudsser Azam, Rinki Minakshi
Pathogenic microbes routinely keep encountering different types of stress in their environment such as high osmolarity, high temperature, pH fluctuations in host gut etc. They tend to acquire certain small molecular weight molecules, termed osmolytes, so as to handle these challenges and survive despite them. These organic osmolytes even at higher concentrations are quite compatible with most of their ongoing intracellular processes. These osmolytes include some which are self-synthesized by the microorganisms, while majority of them are imbibed from the external environment via osmolyte transporters...
June 24, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29938616/the-role-of-e-cadherin-in-helicobacter-pylori-related-gastric-diseases
#11
Yunzhan Zhang, Yunkai Dai, Ruliu Li, Yong Gao, Ling Hu
Helicobacter pylori (H. pylori)-related gastric diseases are a series of gastric mucosal disorders associated with H. pylori infection, including chronic gastritis, gastric ulcer and gastric cancer (GC) etc. The formation of GC is widely believed to be a multistep process, evolving from gastritis and gastric ulcer. Thus, to explore the mechanisms of gastric mucosa from benign to malignant pathological evolution process is the crux of prevention and treatment of GC. As an important adhesion molecule of epithelial cells, E-cadherin plays a key role in the development of gastric diseases...
June 24, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29886827/amino-acid-metabolism-in-dairy-cows-and-their-regulation-in-milk-synthesis
#12
Feiran Wang, Haitao Shi, Shuxiang Wang, Yajing Wang, Zhijun Cao, Shengli Li
Reducing dietary crude protein (CP) and supplementing with certain amino acids (AAs) has been known as a potential solution to improve nitrogen (N) efficiency in dairy production. Thus understanding how AAs are utilized in various sites along the gut is critical. AA flow from the intestine to portal-drained viscera (PDV) and liver then to the mammary gland was elaborated in this article. Recoveries in individual AA in PDV and liver seem to share similar AA pattern with input: output ratio in mammary gland, which subdivides essential AA (EAA) into two groups, lysine (Lys) and branched-chain AA (BCAA) in group 1, input: output ratio > 1; methionine (Met), histidine (His), phenylalanine (Phe) etc...
June 10, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29886826/the-therapeutic-role-of-xenobiotic-nuclear-receptors-against-metabolic-syndrome
#13
Shuqi Pu, Xiaojie Wu, Xiaoying Yang, Yunzhan Zhang, Yunkai Dai, Yueling Zhang, Xiaoting Wu, Yan Liu, Xiaona Cui, Haiyong Jin, Jianhong Cao, Ruliu Li, Jiazhong Cai, Qizhi Cao, Ling Hu, Yong Gao
Xenobiotic nuclear receptors (XNRs) are nuclear receptors that characterized by coordinately regulating the expression of genes encoding drug-metabolizing enzymes and transporters to essentially eliminate and detoxify xenobiotics and endobiotics from the body, including the peroxisome proliferator-activated receptor (PPAR), the farnesoid X receptor (FXR), the liver X receptor (LXR), the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). Heretofore, increasing evidences have suggested that these five XNRs are not only involved in the regulation of xeno-/endo-biotics detoxication but also the development of human diseases, such as cancer, obesity and diabetes...
June 10, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29886825/recent-advances-in-gold-nanoformulations-for-cancer-therapy
#14
Maxim Shevtsov, Yang Zhou, William Khachatryan, Gabriele Multhoff, Huile Gao
Nanotechnology based diagnostic and therapeutic approaches have attracted great interest in oncology over the last few years. Especially gold (Au)-based nanoformulations have gained a lot of attention in cancer detection, therapy and monitoring of outcome. The current report provides a summary of methods how to prepare different types of synthetic gold nanoformulations and their potential applications in boosting photothermal and photodynamic tumor therapies and in radiosensitization.
June 10, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29807513/failure-of-chemotherapy-in-hepatocellular-carcinoma-due-to-impaired-and-dysregulated-primary-liver-drug-metabolizing-enzymes-and-drug-transport-proteins-what-to-do
#15
Salman Ul Islam, Muhammad Bilal Ahmed, Adeeb Shehzad, Mazhar Ul-Islam, Young Sup Lee
BACKGROUND: Most of the drugs are metabolized in the liver by the action of drug metabolizing enzymes. In hepatocellular carcinoma (HCC), primary drug metabolizing enzymes are severely dysregulated, leading to failure of chemotherapy. Sorafenib is the only standard systemic drug available, but it still presents certain limitations, and much effort is required to understand who is responsive and who is refractory to the drug. Preventive and therapeutic approaches other than systemic chemotherapy include vaccination, chemoprevention, liver transplantation, surgical resection, and locoregional therapies...
May 28, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29807512/hypoxia-plays-a-key-role-in-the-pharmacokinetic-changes-of-drugs-at-high-altitude
#16
Xuejiao Zhou, Yongqiong Nian, Yijie Qiao, Meng Yang, Yuanyao Xin, Xiangyang Li
Hypoxia can alter the pharmacokinetic (PK) characteristics of drugs, thereby affecting drug absorption, distribution, metabolism, and excretion. Environmental characteristics at high altitude include but are not limited to hypobaric hypoxia, low temperature, high solar radiation, and arid climate, all of which can adversely affect normal bodily functions. Recent studies have indicated that hypoxia may play a key role in the PK changes of drugs at high altitude. Here we reported the effects of hypoxia on drug metabolism at high altitude, elaborated on the metabolic characteristics of some drugs and the activity and expression of drug-metabolizing enzymes in high-altitude hypoxic environments, and discussed the relevant mechanisms...
May 28, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29804525/a-review-on-the-expression-and-metabolic-features-of-orphan-human-cytochrome-p450-2s1-cyp2s1
#17
Pan Yan, Ong Chin Eng, Chieng Jin Yu
BACKGROUND: Cytochrome P450 2S1 (CYP2S1) is one of the 'orphan' CYPs, which is expressed primarily among extra-hepatic tissues and it is inducible by dioxin. Although the contribution of extra-hepatic CYPs in drug metabolism is considered less significant, they play more important roles in leading to in situ toxicity in organs with higher expression. METHOD: A non-systemic search was performed to review articles relevant to CYP2S1 in literature. This review will update the findings related to the expression and regulation of CYP2S1 gene and protein, substrate profiles and metabolism mechanisms, genetic polymorphisms, and their association with diseases...
May 27, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29788885/application-of-traditional-chinese-herbal-medicine-by-products-as-dietary-feed-supplements-and-antibiotic-replacements-in-animal-production
#18
Abedin Abdallah, Pei Zhang, Qingzhen Zhong, Zewei Sun
Misuse of synthetic antibiotics in livestock leads to the transfer of antibiotic resistant pathogens into humans and deposits toxic residues in meat and milk. There is therefore an urgent need for safe and viable alternative approaches to improve the nutrition and wellbeing of farm animals. An alternative source that has been widely exploited is traditional Chinese herbal medicine (TCHM). These herbal medicines are an important part of the healthcare system in many Asian countries. Such herbs contain several but less toxic bioactive compounds which are generally regarded biodegradable...
May 22, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29788884/progress-of-oral-insulin-and-related-drug-delivery-systems-and-their-pharmacokinetics
#19
Jingjing Chen, Rui Liu, Changxiao Liu, Xin Jin, Qinghua Zhang, Jialu Wang, Fang Zhao, Ze Wang, Haiyan Qiu, Yazhuo Li, Xiulin Yi
BACKGROUND: As society has developed and living standards have improved, diabetes has become a severe public health issue. Insulin plays a crucial role in managing hyperglycemia caused by type I diabetes and particular type II diabetes. Many researchers are seeking alternative, more acceptable methods of insulin delivery, such as oral insulin. An oral formulation has become a new goal for insulin delivery in recent years. METHODS: The PubMed and CNKI databases were searched for "oral insulin, " "drug delivery systems, " and "pharmacokinetics, " and 85 relevant articles were selected from the results as material for this review...
May 22, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29788883/models-of-drug-induced-liver-injury-dili-current-issues-and-future-perspectives
#20
Lucija Kuna, Ivana Bozic, Tomislav Kizivat, Kristina Bojanic, Margareta Mrso, Edgar Kralj, Robert Smolic, George Y Wu, Martina Smolic
Drug-induced liver injury (DILI) is an important cause of acute liver failure cases in the United States, and remains a common cause of withdrawal of drugs in both preclinical and clinical phases. In this article, we review the existing knowledge of appropriate models to study DILI in vitro and in vivo with special focus on hepatic cell models, variations of 3D co-cultures, animal models, databases and predictive modeling and translational biomarkers developed to understand the mechanisms and pathophysiology of DILI...
May 22, 2018: Current Drug Metabolism
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