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Drug Metabolism Reviews

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https://www.readbyqxmd.com/read/30343607/mechanistic-investigation-of-resistance-via-drug-inactivating-enzymes-in-mycobacterium-tuberculosis
#1
Aanchal Kashyap, Pankaj Kumar Singh, Om Silakari
Tuberculosis (TB) is a serious major health concern that has existed from millennia. According to annual WHO report 2016, it is considered as world's ninth highest killer disease by single infectious agent, ranking above HIV/AIDS. To worsen the scenario the development of multi-drug resistant tuberculosis (MDR-TB) and extremely drug resistant tuberculosis (XDR-TB) have significantly reduced the success rate of TB treatment. Several efforts are being made to handle pharmacodynamic resistance (MDR and XDR-TB) involving designing of new inhibitors, targeting mutated target or by multi-targeting agents...
October 20, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/30270675/subcellular-drug-distribution-mechanisms-and-roles-in-drug-efficacy-toxicity-resistance-and-targeted-delivery
#2
Qiao Li, Ting Zhou, Fei Wu, Na Li, Rui Wang, Qing Zhao, Yue-Ming Ma, Ji-Quan Zhang, Bing-Liang Ma
After administration, drug molecules usually enter target cells to access their intracellular targets. In eukaryotic cells, these targets are often located in organelles, including the nucleus, endoplasmic reticulum, mitochondria, lysosomes, Golgi apparatus, and peroxisomes. Each organelle type possesses unique biological features. For example, mitochondria possess a negative transmembrane potential, while lysosomes have an intraluminal delta pH. Other properties are common to several organelle types, such as the presence of ATP-binding cassette (ABC) or solute carrier-type (SLC) transporters that sequester or pump out xenobiotic drugs...
September 29, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/30227749/gut-microbiota-modulates-drug-pharmacokinetics
#3
Juanhong Zhang, Junmin Zhang, Rong Wang
Gut microbiota, one of the determinants of pharmacokinetics, has long been underestimated. It is now generally accepted that the gut microbiota plays an important role in drug metabolism during enterohepatic circulation either before drug absorption or through various microbial enzymatic reactions in the gut. In addition, some drugs are metabolized by the intestinal microbiota to specific metabolites that cannot be formed in the liver. More importantly, metabolizing drugs through the gut microbiota prior to absorption can alter the systemic bioavailability of certain drugs...
September 19, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/30221555/alterations-of-drug-metabolizing-enzymes-and-transporters-under-diabetic-conditions-what-is-the-potential-clinical-significance
#4
Feng Chen, De-Yi Li, Bo Zhang, Jie-Yu Sun, Fang Sun, Xing Ji, Jin-Chun Qiu, Robert B Parker, S Casey Laizure, Jing Xu
There will be 642 million people worldwide by 2040 suffering from diabetes mellitus. Long-term multidrug therapy aims to achieve normal glycemia and minimize complications, and avoid severe hypoglycemic events. The appreciation of the drug-metabolizing enzymes and drug transporters as critical players in the treatment of diabetes has attracted much attention regarding their potential alterations in the pathogenesis of the disease. This review discusses pharmacokinetics-based alterations of cytochrome P450 enzymes, phase-II metabolizing enzymes, and membrane transporter proteins, as well as the potential mechanisms underlying these alterations...
September 16, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/30010437/insights-into-the-intestinal-bacterial-metabolism-of-flavonoids-and-the-bioactivities-of-their-microbe-derived-ring-cleavage-metabolites
#5
Xinchi Feng, Yang Li, Mahmood Brobbey Oppong, Feng Qiu
Flavonoids are a group of phytochemicals widely distributed in plants, fruits, and vegetables that possess numerous bioactivities. After oral administration, flavonoids can be metabolized by the intestinal bacteria into a wide range of low-molecular-weight phenolic acids. In this review, the intestinal bacterial metabolic pathways of different flavonoids (flavones, isoflavones, flavonols, flavanones, and chalcones) and the bioactivities of their microbe-derived ring cleavage metabolites are summarized. Flavonoids undergo different intestinal bacterial metabolic reactions, depending on the characteristics of their structure...
July 16, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/30009643/the-mesentery-an-adme-perspective-on-a-new-organ
#6
Aneesh A Argikar, Upendra A Argikar
With the inclusion of mesentery, the total number of human organs has recently increased by one. The mesentery was formerly construed to be a complex, discontinuous anatomical structure simply serving as a support for organs in abdominal cavity. However, recent research has established the mesentery to be a far more simple and unfragmented organ. Newly emerging information on the mesentery has challenged some older pathophysiological concepts. This review briefly discusses the anatomy of the mesentery, historical perspective on the mesentery, embryology, drug metabolizing enzymes and transporters of the mesentery, and the mesentery's role in diseases...
July 16, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29954222/biotransformation-and-bioactivation-reactions-2017-literature-highlights
#7
S Cyrus Khojasteh, Grover P Miller, Kaushik Mitra, Ivonne M C M Rietjens
This annual review is the third one to highlight recent advances in the study and assessment of biotransformations and bioactivations ( Table 1 ). We followed the same format as the previous years with selection and authoring each section (see Baillie et al. 2016 ; Khojasteh et al. 2017 ). We acknowledge that many universities no longer train students in mechanistic biotransformation studies reflecting a decline in the investment for those efforts by public funded granting institutions. We hope this work serves as a resource to appreciate the knowledge gained each year to understand and hopefully anticipate toxicological outcomes dependent on biotransformations and bioactivations...
June 28, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29540067/the-synthetic-cathinone-%C3%AE-pyrrolidinovalerophenone-%C3%AE-pvp-pharmacokinetic-and-pharmacodynamic-clinical-and-forensic-aspects
#8
REVIEW
Leandro Nóbrega, Ricardo Jorge Dinis-Oliveira
New psychoactive substances (NPS), often referred as 'legal highs' or 'designer drugs', are derivatives and analogs of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse. This work aims to review the state-of-the-art regarding chemical, molecular pharmacology, and in vitro and in vivo data on toxicokinetics of the potent synthetic cathinone α-pyrrolidinovalerophenone (α-PVP or flakka or zombie drug). Chemical, pharmacological, toxicological, and clinical effects of α-PVP were searched in PubMed (U...
May 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29455551/effects-of-5-aza-2-deoxycytidine-decitabine-on-gene-expression
#9
REVIEW
Ratnam S Seelan, Partha Mukhopadhyay, M Michele Pisano, Robert M Greene
5-Aza-2'-deoxycytidine (AzaD), also known as Decitabine, is a deoxycytidine analog that is typically used to activate methylated and silenced genes by promoter demethylation. However, a survey of the scientific literature indicates that promoter demethylation may not be the only (or, indeed, the major) mechanism by which AzaD affects gene expression. Regulation of gene expression by AzaD can occur in several ways, including some that are independent of DNA demethylation. Results from several studies indicate that the effect of AzaD on gene expression is highly context-dependent and can differ for the same gene under different environmental settings...
May 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29451034/cytochrome-p450-in-the-central-nervous-system-as-a-therapeutic-target-in-neurodegenerative-diseases
#10
REVIEW
Cynthia Navarro-Mabarak, Rafael Camacho-Carranza, Jesús Javier Espinosa-Aguirre
Cytochromes P450 (CYPs) constitute a family of enzymes that can be found in the endoplasmic reticulum (ER), mitochondria or the cell surface of the cells. CYPs are characterized by carrying out the oxidation of organic compounds and they are mainly recognized as mediators of the biotransformation of xenobiotics to polar hydrophilic metabolites that can be eliminated from the organism. However, these enzymes play a key role in many other physiological processes, being involved in diverse indispensable metabolic pathways since they metabolize many endogenous substrates...
May 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29390894/difference-and-alteration-in-pharmacokinetic-and-metabolic-characteristics-of-low-solubility-natural-medicines
#11
REVIEW
Shenglei Yan, Yuying Liu, Jianfang Feng, Hua Zhao, Zhongshu Yu, Jing Zhao, Yao Li, Jingqing Zhang
Drug metabolism plays vital roles in the absorption and pharmacological activity of poorly soluble natural medicines. It is important to choose suitable delivery systems to increase the bioavailability and bioactivity of natural medicines with low solubility by regulating their metabolism and pharmacokinetics. This review investigates recent developments about the metabolic and pharmacokinetic behavior of poorly soluble natural medicines and their delivery systems. Delivery systems, dosage, administration route and drug-drug interactions alter the metabolic pathway, and bioavailability of low-solubility natural medicines to different degrees...
May 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29258340/nat1-genotypic-and-phenotypic-contribution-to-urinary-bladder-cancer-risk-a-systematic-review-and-meta-analysis
#12
REVIEW
Hassan R Dhaini, Bassam El Hafi, Assem M Khamis
N-acetyltransferase 1 (NAT1), a polymorphic Phase II enzyme, plays an essential role in metabolizing heterocyclic and aromatic amines, which are implicated in urinary bladder cancer (BCa). This systematic review investigates a possible association between the different NAT1 genetic polymorphisms and BCa risk. Medline, PubMed, EMBASE, Scopus, Web of Science, OpenGrey, and BASE databases were searched to identify eligible studies. The random-effect model was used to calculate pooled effects estimates. Statistical heterogeneity was tested with Chi-square and I2 ...
May 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29258334/a-comprehensive-review-of-recent-studies-on-pharmacokinetics-of-traditional-chinese-medicines-2014-2017-and-perspectives
#13
REVIEW
Peiying Shi, Xinhua Lin, Hong Yao
Traditional Chinese medicines (TCMs) have a long history for safely treating human diseases. Unlike western medicine, TCMs usually contain multiple components synergistically and holistically acting on the diseases. It remains a big challenge to represent rationally the in vivo process of multiple components of TCMs for understanding the relationship between administration and therapeutic effects. For years, efforts were always made to face the challenge, and the achievements were obvious. Here, we give an comprehensive overview of the recent investigation progress (from 2015 to 2017, except the part of 'integrated pharmacokinetics of TCMs' from 2014 to 2017 and the part of 'reverse pharmacokinetics in drug discovery from natural medicines' in 2014) on pharmacokinetics of TCMs, mainly referring to the following six aspects: (1) classical pharmacokinetic studies on TCMs; (2) absorbed components and metabolites identification of TCMs; (3) pharmacokinetic herb-drug interactions and herb-herb interactions with TCMs; (4) integrated pharmacokinetics of TCMs; (5) pharmacokinetic and pharmacodynamic combination studies to dissect the action mechanisms of TCMs; and (6) reverse pharmacokinetics in drug discovery from natural medicines...
May 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29254370/effect-of-cardiopulmonary-bypass-on-cytochrome-p450-enzyme-activity-implications-for-pharmacotherapy
#14
REVIEW
Santosh Kumar Sreevatsav Adiraju, Kiran Shekar, John F Fraser, Maree T Smith, Sussan Ghassabian
For patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, there are well-documented changes in the pharmacokinetics (PK) of commonly administered drugs. Although multiple factors potentially underpin these changes, there has been scant research attention on the impact of CPB to alter the activities of cytochrome P450 (CYP) isoenzymes. PK changes during cardiac surgery with CPB have the potential to adversely affect the safety and efficacy of pharmacotherapy and increase the risk of drug-drug interactions...
May 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29390908/towards-a-better-understanding-of-the-cannabinoid-related-orphan-receptors-gpr3-gpr6-and-gpr12
#15
REVIEW
Paula Morales, Israa Isawi, Patricia H Reggio
GPR3, GPR6, and GPR12 are three orphan receptors that belong to the Class A family of G-protein-coupled receptors (GPCRs). These GPCRs share over 60% of sequence similarity among them. Because of their close phylogenetic relationship, GPR3, GPR6, and GPR12 share a high percentage of homology with other lipid receptors such as the lysophospholipid and the cannabinoid receptors. On the basis of sequence similarities at key structural motifs, these orphan receptors have been related to the cannabinoid family. However, further experimental data are required to confirm this association...
February 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29390896/targeting-the-endocannabinoid-system-as-a-potential-anticancer-approach
#16
REVIEW
Rico Schwarz, Robert Ramer, Burkhard Hinz
The endocannabinoid system is currently under intense investigation due to the therapeutic potential of cannabinoid-based drugs as treatment options for a broad variety of diseases including cancer. Besides the canonical endocannabinoid system that includes the cannabinoid receptors CB1 and CB2 and the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, recent investigations suggest that other fatty acid derivatives, receptors, enzymes, and lipid transporters likewise orchestrate this system as components of the endocannabinoid system when defined as an extended signaling network...
February 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29385930/pro-psychotic-effects-of-synthetic-cannabinoids-interactions-with-central-dopamine-serotonin-and-glutamate-systems
#17
REVIEW
William E Fantegrossi, Catheryn D Wilson, Michael D Berquist
An association between marijuana use and schizophrenia has been noted for decades, and the recent emergence of high-efficacy synthetic cannabinoids (SCBs) as drugs of abuse has lead to a growing number of clinical reports of persistent psychotic effects in users of these substances. The mechanisms underlying SCB-elicited pro-psychotic effects is unknown, but given the ubiquitous neuromodulatory functions of the endocannabinoid system, it seems likely that agonist actions at cannabinoid type-1 receptors (CB1Rs) might modulate the functions of other neurotransmitter systems known to be involved in schizophrenia...
February 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29378464/preface-to-dmr-special-edition-cannabinoid-receptors-and-ligands-therapeutic-drug-development-and-abuse-potential
#18
Paul L Prather
No abstract text is available yet for this article.
February 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29376443/old-and-new-synthetic-cannabinoids-lessons-from-animal-models
#19
REVIEW
Mary Tresa Zanda, Liana Fattore
Synthetic cannabinoids have long been studied for their therapeutic potentials. However, during the last decade, new generations of synthetic cannabinoid agonists appeared on the drug market. These new psychoactive substances are currently sold as 'marijuana-like' products as they claim to mimic the effects of the psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC). Yet, their effects are more intense and potent than THC, typically last longer and are often associated to serious psychiatric consequences...
February 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29355038/the-future-of-type-1-cannabinoid-receptor-allosteric-ligands
#20
Mariam Alaverdashvili, Robert B Laprairie
Allosteric modulation of the type 1 cannabinoid receptor (CB1R) holds great therapeutic potential. This is because allosteric modulators do not possess intrinsic efficacy, but instead augment (positive allosteric modulation) or diminish (negative allosteric modulation) the receptor's response to endogenous ligand. Consequently, CB1R allosteric modulators have an effect ceiling which allows for the tempering of CB1R signaling without the desensitization, tolerance, dependence, and psychoactivity associated with orthosteric compounds...
February 2018: Drug Metabolism Reviews
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