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Drug Metabolism Reviews

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...
December 19, 2017: Drug Metabolism Reviews
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...
December 19, 2017: Drug Metabolism Reviews
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...
December 19, 2017: Drug Metabolism Reviews
Jing Gu, Zheng Sui, Chunshu Fang, Qunyou Tan
The vast majority of chemical drugs or drug candidates contain stereocenter(s) in their molecular structures. In these molecules, stereochemical properties are vital properties that influence or even determine their drug actions. Therefore, studying the stereochemical issues of drugs (or drug candidates) is necessary for rational drug use. These stereochemical issues are usually involved with the stereoselectivity in pharmacokinetic processes, especially in the metabolism process. Thus, the investigation of the stereochemical issues in drug metabolism process deserves great attention, especially in those chiral/prochiral antineoplastic agents exhibiting pharmacodynamics and toxicologic differences between stereoisomers...
October 27, 2017: Drug Metabolism Reviews
Mei Zeng, Lan Yang, Dan He, Yao Li, Mingxin Shi, Jingqing Zhang
Drug metabolism plays an important role in the drug disposal process. Differences in pharmacokinetics among individuals are the basis for personalized medicine. Natural medicines, formed by long-term evolution of nature, prioritize the action of a target protein with a drug. Natural medicines are valued for structural diversity, low toxicity, low cost, and definite biological activities. Metabolic pathway and pharmacokinetic research of natural medicines is highly beneficial for clinical dose adjustment and the development of personalized medicine...
September 14, 2017: Drug Metabolism Reviews
Ricardo Jorge Dinis-Oliveira
Anxiolytic drugs, namely benzodiazepines, are the most commonly used psychoactive substances since anxiety disorders are prevalent mental disorders particularly in the Western world. Oxazepam is a short-acting benzodiazepine and one of the most frequently prescribed anxiolytic drugs. It is also the active metabolite of a wide range of other benzodiazepines, such as diazepam, ketazolam, temazepam, chlordiazepoxide, demoxazepam, halazepam, medazepam, prazepam, pinazepam, and chlorazepate. Therefore, relevant clinical and forensic outocomes may arise, namely those related to interference in driving performance...
September 14, 2017: Drug Metabolism Reviews
Xu Wang, Qinghua Wu, Aimei Liu, Arturo Anadón, José-Luis Rodríguez, María-Rosa Martínez-Larrañaga, Zonghui Yuan, María-Aránzazu Martínez
Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress...
August 16, 2017: Drug Metabolism Reviews
Sofía López-Gil, Natalia Nuño-Lámbarri, Norberto Chávez-Tapia, Misael Uribe, Varenka J Barbero-Becerra
Mexico owns approximately 4500 medicinal plants species, a great diversity that position it at the second place after China. According to the Mexican health department, 90% of common population consumes them to treat various diseases. Additionally, herbal remedies in Latin America (LA) are considered a common practice, but the frequency of use and the liver damage related to its consumption is still unknown. Despite the high prevalence and indiscriminate herbal consumption, the exact mechanism of hepatotoxicity and adverse effects is not fully clarified and is still questioned...
August 2017: Drug Metabolism Reviews
Krishnamoorthy Mohana, Anant Achary
Glutathione-S-transferase (GST) inhibition is a strategy to overcome drug resistance. Several isoforms of human GSTs are present and they are expressed in almost all the organs. Specific expression levels of GSTs in various organs are collected from the human transcriptome data and analysis of the organ-specific expression of GST isoforms is carried out. The variations in the level of expressions of GST isoforms are statistically significant. The GST expression differs in diseased conditions as reported by many investigators and some of the isoforms of GSTs are disease markers or drug targets...
July 12, 2017: Drug Metabolism Reviews
Natalia Marto, Judit Morello, Emilia C Monteiro, Sofia A Pereira
The interindividual variability in drug response is a major issue in clinical practice and in drug development. Sulfoconjugation is an important Phase II reaction catalyzed by cytosolic sulfotransferases (SULTs), playing a major role in homeostatic functions, xenobiotic detoxification, and carcinogen bioactivation. SULT display wide interindividual variability, explained only partially by genetic variation, suggesting that other non-genetic, epigenetic, and environmental influences could be major determinants of variability in SULT activity...
June 20, 2017: Drug Metabolism Reviews
Emilie Darrigues, Vijayalakshmi Dantuluri, Zeid A Nima, Kieng Bao Vang-Dings, Robert J Griffin, Alexandru R Biris, Anindya Ghosh, Alexandru S Biris
Raman spectroscopy and surface-enhanced raman scattering (SERS) have the potential to improve the detection and monitoring of various diseases, particularly cancer, with or without the support of multifunctional active nanosystems. This review is focused on the recent advances that have made Raman a major tool for treatment guidance for surgical tumor resection or for analytical monitoring of various therapies, such as photodynamic therapy, photothermal therapy, and drug delivery. The potential of Raman spectroscopy and nanosytems to further improve cancer treatments is also discussed...
June 19, 2017: Drug Metabolism Reviews
Emilie Darrigues, Zeid A Nima, Waqar Majeed, Kieng Bao Vang-Dings, Vijayalakshmi Dantuluri, Alexandru R Biris, Vladimir P Zharov, Robert J Griffin, Alexandru S Biris
Optical techniques, including Raman, photothermal and photoacoustic microscopy and spectroscopy, have been intensively explored for the sensitive and accurate detection of various diseases. Rapid advances in lasers, photodetectors, and nanotechnology have led to the development of Raman spectroscopy, particularly surface-enhanced Raman scattering (SERS), as a promising imaging modality that can help diagnose many diseases. This review focuses on the major recent advances in Raman spectroscopy and SERS-enhancing contrast nanoagents, as well as their potential to transition from a proof-of-concept approach to a cancer detection tool in vitro and in vivo...
June 15, 2017: Drug Metabolism Reviews
S Cyrus Khojasteh, Ivonne M C M Rietjens, Deepak Dalvie, Grover Miller
We are pleased to present a second annual issue highlighting a previous year's literature on biotransformation and bioactivation. Each contributor to this issue worked independently to review the articles published in 2016 and proposed three to four articles, which he or she believed would be of interest to the broader research community. In each synopsis, the contributing author summarized the procedures, analyses and conclusions as described in the original manuscripts. In the commentary sections, our authors offer feedback and highlight aspects of the work that may not be apparent from an initial reading of the article...
May 31, 2017: Drug Metabolism Reviews
Upendra A Argikar, Jennifer L Dumouchel, Christine E Dunne, Andrea J Bushee
Metabolism in the eye for any species, laboratory animals or human, is gaining rapid interest as pharmaceutical scientists aim to treat a wide range of so-called incurable ocular diseases. Over a period of decades, reports of metabolic activity toward various drugs and biochemical markers have emerged in select ocular tissues of animals and humans. Ocular cytochrome P450 (P450) enzymes and transporters have been recently reviewed. However, there is a dearth of collated information on non-P450 drug metabolizing enzymes in eyes of various preclinical species and humans in health and disease...
May 17, 2017: Drug Metabolism Reviews
Enoch Cobbina, Fatemeh Akhlaghi
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. It is defined by the presence of steatosis in more than 5% of hepatocytes with little or no alcohol consumption. Insulin resistance, the metabolic syndrome or type 2 diabetes and genetic variants of PNPLA3 or TM6SF2 seem to play a role in the pathogenesis of NAFLD. The pathological progression of NAFLD follows tentatively a "three-hit" process namely steatosis, lipotoxicity and inflammation. The presence of steatosis, oxidative stress and inflammatory mediators like TNF-α and IL-6 has been implicated in the alterations of nuclear factors such as CAR, PXR, PPAR-α in NAFLD...
May 2017: Drug Metabolism Reviews
Guangyi Yang, Shufan Ge, Rashim Singh, Sumit Basu, Katherine Shatzer, Ming Zen, Jiong Liu, Yifan Tu, Chenning Zhang, Jinbao Wei, Jian Shi, Lijun Zhu, Zhongqiu Liu, Yuan Wang, Song Gao, Ming Hu
Glucuronidation is a well-recognized phase II metabolic pathway for a variety of chemicals including drugs and endogenous substances. Although it is usually the secondary metabolic pathway for a compound preceded by phase I hydroxylation, glucuronidation alone could serve as the dominant metabolic pathway for many compounds, including some with high aqueous solubility. Glucuronidation involves the metabolism of parent compound by UDP-glucuronosyltransferases (UGTs) into hydrophilic and negatively charged glucuronides that cannot exit the cell without the aid of efflux transporters...
May 2017: Drug Metabolism Reviews
Ivanna Hrynchak, Emília Sousa, Madalena Pinto, Vera Marisa Costa
Anticancer drugs are presently guarantying more survivors as a result of more powerful drugs or combinations of drugs used in therapy. Thus, it has become more crucial to study and overcome the side effects of these therapies. Cardiotoxicity is one of the most relevant side effects on the long-term cancer survivors, because of its high social and economic impact. Drug metabolism can result in active metabolites or toxic metabolites that can lead to important side effects. The metabolites of anticancer drugs are possible culprits of cardiotoxicity; however, the cardiotoxicity of many of the metabolites in several drug classes was not yet suitably studied so far...
April 25, 2017: Drug Metabolism Reviews
Kun Wang, Xinchi Feng, Liwei Chai, Shijie Cao, Feng Qiu
Berberine, a bioactive alkaloid isolated from several herbal substances, possesses multiple pharmacological effects, including antimicrobial, antidiabetic, anticancer activities. Meanwhile, berberine undergoes extensive metabolism after oral administration which results in its extremely low plasma exposure. Therefore, it is believed that the metabolites of berberine also contribute a lot to its pharmacological effects. Along these lines, this review covers the metabolism studies of berberine in terms of its metabolic pathways and metabolic organs based on the identified metabolites, and it also covers the pharmacological activities of its active metabolites...
April 3, 2017: Drug Metabolism Reviews
Ricardo Jorge Dinis-Oliveira
Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT)2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor psychoactive metabolites...
February 2017: Drug Metabolism Reviews
Dragos Apostu, Ondine Lucaciu, Gheorghe Dan Osvald Lucaciu, Bogdan Crisan, Liana Crisan, Mihaela Baciut, Florin Onisor, Grigore Baciut, Radu Septimiu Câmpian, Simion Bran
Titanium implants are widely used on an increasing number of patients in orthopedic and dental medicine. Despite the good survival rates of these implants, failures that lead to important socio-economic consequences still exist. Recently, research aimed at improving implant fixation, a process called osseointegration, has focused on a new, innovative field: systemic delivery of drugs. Following implant fixation, patients receive systemic drugs that could either impair or enhance osseointegration; these drugs include anabolic and anti-catabolic bone-acting agents in addition to new treatments...
February 2017: Drug Metabolism Reviews
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