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Drug Metabolism Reviews

Seyyed Mojtaba Mousavi, Seyyed Alireza Hashemi, Younes Ghasemi, Ali Mohammad Amani, Aziz Babapoor, Omid Arjmand
In this Review article, recent progress progress in matter of graphene oxide (GO) synthesis and its functionalization via a vast range of materials, including small molecules, polymers, and biomolecules, were reported and systematically summarized in order to overcome the inherent drawbacks of GO nanocarriers and thereby make these nanocarriers suitable for delivering chemotherapeutic agents, genes, and short interfering RNAs. Briefly, this work describes current strategies for the large scale production of GO and modification of graphene-based nanocarriers surfaces through practical chemical approaches, improving their biocompatibility and declining their toxicity...
February 11, 2019: Drug Metabolism Reviews
Aline T Marinho, Joana P Miranda, Umbelina Caixas, Catarina Charneira, Clara Gonçalves-Dias, M Matilde Marques, Emilia C Monteiro, Alexandra M M Antunes, Sofia A Pereira
Nevirapine (NVP) is a 1st generation non-nucleoside reverse transcriptase inhibitor widely used for the treatment and prophylaxis of human immunodeficiency virus infection. The drug is taken throughout the patient´s life and, due to the availability of an extendend release formulation, it is administered once daily. This antiretroviral is one of the scarce examples of drugs with prescrition criteria based on sex, in order to prevent adverse reactions. The therapy with NVP has been associated with potentially life-threatening liver and idiosyncratic skin toxicity...
February 3, 2019: Drug Metabolism Reviews
Dragos Apostu, Ondine Lucaciu, Alexandru Mester, Horea Benea, Daniel Oltean-Dan, Florin Onisor, Mihaela Baciut, Simion Bran
Bone is a complex tissue of the with unique properties such as high strength and regeneration capabilities while carrying out multiple functions. Bone regeneration occurs both in physiological situations (bone turnover) and pathological situations (e.g. fractures), being performed by osteoblasts and osteoclasts. If this process is inadequate, fracture nonunion or aseptic loosening of implants occurs and requires a complex treatment. Exogenous factors are currently used to increase bone regeneration process when needed, such as bisphosphonates and vitamin D, but limitations do exist...
January 31, 2019: Drug Metabolism Reviews
Ilse du Preez, Du Toit Loots
The World Health Organization recommends the directly observed therapy short-course (DOTS) regimen, a combination of four first-line antibiotics (isoniazid, rifampicin, pyrazinamide and ethambutol), for the treatment of active pulmonary tuberculosis (TB). However, despite the fact that this treatment regimen is commonly used worldwide, the metabolism and anti-bacterial mechanisms of these drugs are not yet fully understood. This lack of information ultimately contributes to the poor patient compliance and the subsequent treatment failure and post treatment relapse seen in some TB patients...
December 17, 2018: Drug Metabolism Reviews
Amaj Ahmed Laskar, Hina Younus
Aldehydes are carbonyl compounds found ubiquitously in the environment, derived from both natural and anthropogenic sources. As the aldehydes are reactive species, therefore, they are generally toxic to the body. To reduce the toxicity and pathogenesis related to aldehydes, the human body contains several aldehyde metabolizing enzyme systems including aldehyde oxidases, cytochrome P450 enzymes, aldo-ketoreductases, alcohol dehydrogenases, short-chain dehydrogenases/reductases and aldehyde dehydrogenases (ALDHs)...
December 4, 2018: Drug Metabolism Reviews
Dan Xu, Songqiang Huang, Hui Wang, Wen Xie
Nuclear receptors (NRs) belong to a family of ligand dependent transcription factors. The target genes of NRs include many drug metabolizing enzymes and transporters. The central nervous system (CNS) bears the expression of NRs, drug metabolizing enzymes and transporters. NRs that express in the brain can be divided into three groups according to their characteristics of ligand binding: steroid hormone receptors, non-steroid hormone receptors, and orphan receptors. The NR-mediated regulation of drug metabolizing enzymes and transporters plays important roles in the metabolism and disposition of drugs in the CNS and the penetration of endogenous and exogenous substances through the blood-brain barrier (BBB)...
December 2, 2018: Drug Metabolism Reviews
Anna Haduch, Władysława Anna Daniel
The current state of knowledge indicates that the cerebral cytochrome P450 (CYP) plays an important role in the endogenous metabolism in the brain. Different CYP isoenzymes mediate metabolism of many endogenous substrates, such as monoaminergic neurotransmitters, neurosteroids, cholesterol, vitamins and arachidonic acid. Therefore, these enzymes may affect brain development, susceptibility to mental and neurodegenerative diseases and may contribute to their pathophysiology. In addition, they can modify the therapeutic effects of psychoactive drugs at the place of their target action in the brain, where the drugs can act by affecting the metabolism of endogenous substrates...
December 2, 2018: Drug Metabolism Reviews
Safeer Khan, Anum Shahzadi
Cachexia not only has a dramatically harmful impact on a patient's life, but also a poor response to therapeutic agents. The purpose of the present review is to provide updated information concerning the pharmacokinetic aspects of drugs used to treat cardiopulmonary cachexia in patients with no signs of hepatic or renal pathology. A systematic search of PubMed, the Cochrane Central Register of Control Trials, Science Direct, and Clinical Trials Registry (, encompassing the period between 2000 and 2017, was conducted in accordance to PRISMA guidelines...
November 18, 2018: Drug Metabolism Reviews
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
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
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
Slobodan P Rendic, F Peter Guengerich
Cytochrome P450 (P450, CYP) enzymes have long been of interest due to their roles in the metabolism of drugs, pesticides, pro-carcinogens, and other xenobiotic chemicals. They have also been of interest due to their very critical roles in the biosynthesis and metabolism of steroids, vitamins, and certain eicosanoids. This review covers the 22 (of the total of 57) human P450s in Families 5-51 and their substrate selectivity. Furthermore, included is information and references regarding inducibility, inhibition, and (in some cases) stimulation by chemicals...
August 2018: Drug Metabolism Reviews
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...
August 2018: Drug Metabolism Reviews
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
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
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
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
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
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
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
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