Systemic drugs with impact on osteoarthritis.
Authors: Apostu D, Lucaciu O, Mester A, Oltean-Dan D, Baciut M, Baciut G, Bran S, Onisor F, Piciu A, Pasca RD, Maxim A, Benea H Abstract Articular cartilage has a complex structure and metabolism which allow for a proper movement within joints. Nevertheless, several systemically administered pharmacological agents have been proved to improve the anabolic response in the case of cartilage lesions. Alendronate, glucosamine, chondroitin sulfate, hyaluronic acid, collagen hydrolysate, vitamin C, vitamin D, aspirin and strontium ranelate have shown positive results in clinical trials. On the other hand, calcitonin, rise...
Source: Drug Metabolism Reviews - November 19, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Current evidence on thyroid related adverse events in patients treated with protein tyrosine kinase inhibitors.
Authors: Gabora K, Piciu A, Bădulescu IC, Larg MI, Stoian IA, Piciu D Abstract Tyrosine kinase inhibitors (TKI) are gaining more ground in oncology, they are widely used in the treatment of multiple types of cancers; still important side effects limit their efficacy. The aim of this study is to evaluate the existing medical literature on TKI induced thyroid dysfunction, to assess the adverse effects of targeted therapy on thyroid function in oncological patients and to evaluate the effects of thyroid dysfunction on disease prognosis. We included in this review 22 original studies published between 2010 and 2019. W...
Source: Drug Metabolism Reviews - November 14, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Ethanol and its metabolites: update on toxicity, benefits, and focus on immunomodulatory effects.
This article summarizes recent experimental and epidemiological data on the toxic and beneficial effects of ethanol and its metabolites (acetaldehyde), and focuses on their immunomodulatory effects. The section dealing with the toxic effects of alcohol focuses on its chronic toxicity (liver disorders, carcinogenic effects, cardiovascular disorders, neuropsychic disorders, addiction and withdrawal syndrome, hematologic disorders, reprotoxicity, osteoporosis) although acute toxicity is considered. The role of oxidative metabolism of ethanol by alcohol dehydrogenase, cytochrome P450 2E1, and aldehyde dehydrogenase, as well as...
Source: Drug Metabolism Reviews - October 27, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Quantifying fetal alcohol exposure by meconium fatty acid ethyl esters (FAEE); association with adverse fetal outcomes and population estimates of fetal alcohol exposure.
Authors: Koren G, Cohen R Abstract Fetal Alcohol Spectrum Disorder (FASD) describes the wide range of adverse physical, behavioral and cognitive effects resulting from ethanol exposure during embryonic and fetal development. Identification of children suffering from FASD is often difficult, as abuse of ethanol during pregnancy is a heavily stigmatized behavior that receives little prenatal screening attention in routine care. Over the last 3 decades, measurement of the ethanol metabolites fatty acid ethyl esters (FAEE) has emerged as a useful tool to detect in the neonatal period fetal alcohol exposure starting fro...
Source: Drug Metabolism Reviews - October 11, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Commercially available bone graft substitutes: the impact of origin and processing on graft functionality.
Authors: Bow A, Anderson DE, Dhar M Abstract Development of effective and cost-efficient bone tissue engineering grafts has been the key area of research for regenerative medicine, yet an ideal grafting material has remained elusive due in large part to the highly dynamic nature of bone. A wide array of materials, both natural and synthetic, have been implemented as potential candidates for commercially available products, yet the gold standard for grafting material still remains autogenous bone. We review currently commercially available bone graft materials and relevant graft characteristics that impact the effec...
Source: Drug Metabolism Reviews - October 4, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

The human organic cation transporter OCT1 and its role as a target for drug responses.
Authors: Brosseau N, Ramotar D Abstract The human organic cation uptake transporter OCT1, encoded by the SLC22A1 gene, is highly expressed in the liver and reported to possess a broad substrate specificity. OCT1 operates by facilitated diffusion and allows the entry of nutrients into cells. Recent findings revealed that OCT1 can mediate the uptake of drugs for treating various diseases such as cancers. The levels of OCT1 expression correlate with the responses towards many drugs and functionally defective OCT1 lead to drug resistance. It has been recently proposed that OCT1 should be amongst the crucial drug target...
Source: Drug Metabolism Reviews - October 1, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Single nucleotide polymorphisms in treatment of polycystic ovary syndrome: a systematic review.
The objective of this systematic review is to review single nucleotide polymorphisms (SNPs) associated with drugs used for the treatment of PCOS to understand pharmacogenetics variability of patients to drug response there by helping clinicians in designing tailored treatments and possibly reducing adverse drug reactions. A comprehensive electronic literature search was conducted to highlight some clinically relevant SNPs that act to influence PCOS and associated co-morbidities. A total of 16 studies were included in this review. These genetic variations can be used as a potential target for pharmacotherapy and pharmacogen...
Source: Drug Metabolism Reviews - September 25, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Aldehyde oxidase at the crossroad of metabolism and preclinical screening.
Authors: Cheshmazar N, Dastmalchi S, Terao M, Garattini E, Hamzeh-Mivehroud M Abstract Human AOX1 is a member of the mammalian aldehyde oxidase (AOX) family of enzymes and it is an emerging cytosolic enzyme involved in phase I drug-metabolism, bio-transforming a number of therapeutic agents and xenobiotics. The current trend in drug-development is to design molecules which are not recognized and inactivated by CYP450 monooxygenases, the main drug-metabolizing system, to generate novel therapeutic agents characterized by optimal pharmacokinetic and pharmacodynamic properties. Unfortunately, this has resulted in a su...
Source: Drug Metabolism Reviews - September 25, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Clinical and genetic predictors of diabetes drug's response.
Authors: Fodor A, Cozma A, Suharoschi R, Sitar-Taut A, Roman G Abstract Diabetes is a major health problem worldwide. Glycemic control is the main goal in the management of type 2 diabetes. While many anti-diabetic drugs and guidelines are available, almost half of diabetic patients do not reach their treatment goal and develop complications. The glucose-lowering response to anti-diabetic drug differs significantly between individuals. Relatively little is known about the factors that might underlie this response. The identification of predictors of response to anti-diabetic drugs is essential for treatment persona...
Source: Drug Metabolism Reviews - August 29, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Bioactivation of herbal constituents: mechanisms and toxicological relevance.
Authors: Wen B, Gorycki P Abstract The increase in the application of herbal medicines and dietary products over the last decades has been accompanied with a substantial increase in case reports of herb-induced toxicities. Metabolic activation of relatively inert functional groups to chemically reactive metabolites is often considered to be an obligatory event in the etiology of drug-induced adverse reactions. Circumstantial evidence suggests that several herb-induced toxicities are a result of transformation of herbal constituents to electrophilic reactive metabolites that can covalently bind to vital macromolecul...
Source: Drug Metabolism Reviews - August 28, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Emerging Frontiers in Drug Release Control by Core-Shell Nanofibers: A Review.
Authors: Monfared M, Taghizadeh S, Zare-Hoseinabadi A, Mousavi SM, Hashemi SA, Ranjbar S, Amani AM Abstract In recent years, core-shell (CS) nanofiber has widely been used as a carrier for controlled drug release. This outstanding attention toward CS nanofiber is mainly due to its tremendous significance in controllable drug release in specific locations. The major advantage of CS nanofibers is forming a highly porous mesh, boosting its performance for many applications, due to its large surface-to-volume ratio. This inherently high ratio has prompted electrospun fibers to be considered one of the best drug-deliver...
Source: Drug Metabolism Reviews - July 13, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Understanding the Basis of Medical Use of Poly-Lactide-Based Resorbable Polymers and Composites - a Review of the Clinical and Metabolic Impact.
Authors: Vacaras S, Baciut M, Lucaciu O, Dinu C, Baciut G, Crisan L, Hedesiu M, Crisan B, Onisor F, Armencea G, Mitre I, Barbur I, Kretschmer W, Bran S Abstract This review intended to comparatively explain and present the most important medical use and biological impact of poly-lactides and lactide-based composites. The utilization and degradation of compounds based on lactic acid and polylactides is described in detail. Understanding the metabolism and degradation phenomenon and the factors that potentially influence it is key to modulating their properties as well as their characteristics driven from the fabrica...
Source: Drug Metabolism Reviews - July 13, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Metabolism of Lysergic Acid Diethylamide (LSD): an update.
Authors: Libânio Osório Marta RF Abstract LSD is the most potent hallucinogen known and its pharmacological effect results from stimulation of central serotonin receptors (5-HT2). Since LSD is seen as physiologically safe compound with low toxicity, its use in therapeutics has been renewed during the last few years. This review aims to discuss LSD metabolism, by presenting all metabolites as well as clinical and toxicological relevance. LSD is rapidly and extensively metabolized into inactive metabolites; whose detection window is higher than parent compound. The metabolite 2-oxo-3-hydroxy LSD is the m...
Source: Drug Metabolism Reviews - July 5, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Novel insights into the complex pharmacokinetics of voriconazole: a review of its metabolism.
Authors: Schulz J, Kluwe F, Mikus G, Michelet R, Kloft C Abstract Voriconazole, a second-generation triazole frequently used for the prophylaxis and treatment of invasive fungal infections, undergoes complex metabolism mainly involving various (polymorphic) cytochrome P450 enzymes in humans. Although high inter- and intraindividual variability in voriconazole pharmacokinetics have been observed and the therapeutic range for this compound is relatively narrow, the metabolism of voriconazole has not been fully elucidated yet. The available literature data investigating the multiple different pathways and metabolites ...
Source: Drug Metabolism Reviews - June 20, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Drug Metabolizing Enzymes-Associated Chemo Resistance and Strategies to Overcome it.
Authors: Verma H, Bahia MS, Choudhary S, Singh PK, Silakari O Abstract Regardless of continuous research to develop effective chemotherapies and improve patient's prognosis, cancer still remains one of the most deadly diseases worldwide. The reduction in the pace of successfully developing an effective anti-cancer drug is due to the rapid emergence of drug resistance exhibited by tumor cells. One of the resistance mechanisms which is least considered and somewhat overlooked is chemoresistance via drug metabolizing enzymes (DMEs). Therefore, this review emphasises on pharmacokinetic resistance specifically the DMEs ...
Source: Drug Metabolism Reviews - June 19, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

The influence of drugs on peripheral nerve regeneration.
Authors: Bota O, Fodor L Abstract Currently there are no established adjuvant drugs for the acceleration of peripheral nerve regeneration. In this paper we reviewed the literature from the last 10 years and described the drugs proved to accelerate the functional and histological regeneration of the peripheral nerves, either after trauma or in neuropathy experimental models. The vast majority of the studies were experimental with very few small clinical studies, which indicates the need for prospective randomized studies to identify the best drugs to use as adjuvants for nerve regeneration. PMID: 31203666 [PubMe...
Source: Drug Metabolism Reviews - June 19, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Acetylenes: cytochrome P450 oxidation and mechanism-based enzyme inactivation.
Authors: Ortiz de Montellano PR Abstract The oxidation of carbon-carbon triple bonds by cytochrome P450 produces ketene metabolites that are hydrolyzed to acetic acid derivatives or are trapped by nucleophiles. In the special case of 17α-ethynyl sterols, D-ring expansion and de-ethynylation have been observed as competing pathways. The oxidation of acetylenic groups is also associated with mechanism-based inactivation of cytochrome P450 enzymes. One mechanism for this inactivation is reaction of the ketene metabolite with cytochrome P450 residues essential for substrate binding or catalysis. However, in the c...
Source: Drug Metabolism Reviews - June 19, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Zinc-Based Metal Organic Frameworks as Nontoxic and Biodegradable Platforms for Biomedical Applications: Review Study.
Authors: Bahrani S, Hashemi SA, Mousavi SM, Azhdari R Abstract Development of biomedical systems for controllable drug delivery systems and construction of biosensors is imperative to reduce side effects of common treatment techniques and enhance the therapeutic efficacy. To address this issue, metal-organic frameworks (MOFs) as hybrid porous polymeric structures have attracted worldwide attention due to their unprecedented opportunities in vast range of applications in diverse fields including chemistry, biological and medicinal science as gas storage/separation, sensing and drug delivery systems. Recently, biomed...
Source: Drug Metabolism Reviews - June 19, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

A Comprehensive Review of Cytochrome P450 2E1 for Xenobiotic Metabolism.
This study presents a timely systematic review on CYP2E1's xenobiotic metabolism, genetic polymorphism, and inhibitors, with the focus on their clinical relevance for the efficacy and toxicity of various CYP2E1 substrates. Moreover, several knowledge gaps have been identified towards fully understanding the potential interactions among different CYP2E1 substrates in clinical settings. Through in-depth analyses of these knowns and unknowns, we expect this review will aid in future drug development and improve the management of CYP2E1 related clinical toxicity. PMID: 31203697 [PubMed - as supplied by publisher] (Source: ...
Source: Drug Metabolism Reviews - June 19, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Nasal odorant metabolism: enzymes, activity and function in olfaction.
Authors: Heydel JM, Faure P, Neiers F Abstract The nasal tissues have the main consecutive roles of moistening and heating the air entering the respiratory tract and detecting odor via the activation of olfactory receptors in the neuro-olfactory epithelium. Initially, nasal toxicology was investigated to better assess the risk of nasal injuries caused by environmental toxicants or their active metabolites. Later, the characterization of the nasal toxicological barrier was a research concern for the purposes of intranasal drug delivery. Both fields allowed for an increase in our knowledge of the nasal xenobiotic-met...
Source: Drug Metabolism Reviews - June 19, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Biotransformation and Bioactivation Reactions - 2018 Literature Highlights.
Authors: Khojasteh SC, Bumpus NN, Driscoll JP, Miller GP, Mitra K, Rietjens IMCM, Zhang D Abstract In the past three decades, ADME sciences have become an integral component of the drug discovery and development process. At the same time, the field has continued to evolve, thus requiring ADME scientists to be knowledgeable of and engage with diverse aspects of drug assessment: from pharmacology to toxicology, and from in silico modeling to in vitro models and finally in vivo models. Progress in this field requires deliberate exposure to different aspects of ADME; however, this task can seem daunting in the current ...
Source: Drug Metabolism Reviews - June 8, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Pharmacokinetic and pharmacodynamic of bupropion: integrative overview of relevant clinical and forensic aspects.
Authors: Costa R, Oliveira NG, Dinis-Oliveira RJ Abstract Bupropion is an atypical antidepressant of the aminoketone group, structurally related to cathinone, associated with a wide interindividual variability. An extensive pharmacokinetics review of bupropion was performed, also focusing on chemical, pharmacological, toxicological, clinical and forensic aspects of this drug without a limiting period. Bupropion is a chiral, basic, highly lipophilic drug, clinically used as racemate that undergoes extensive stereoselective metabolism. Its major active metabolites, hydroxybupropion, threohydrobupropion and erythrohyd...
Source: Drug Metabolism Reviews - May 29, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

A review of phthalate pharmacokinetics in human and rat: what factors drive phthalate distribution and partitioning?
Authors: Domínguez-Romero E, Scheringer M Abstract Phthalates are a class of compounds that have extensively been used as plasticizers in different applications. Several phthalates have been recognized as substances of very high concern (SVHCs) in the EU, because of their toxicity for reproduction. However, high amounts of other phthalates are still produced and imported in the European Economic Area. In China and the US, recent studies show increasing concentrations of several phthalates in the air and in human urine, respectively. The understanding of phthalate absorption, distribution, metabolism and elim...
Source: Drug Metabolism Reviews - May 24, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

The impact of proton pump inhibitors on bone regeneration and implant osseointegration.
Authors: Mester A, Apostu D, Ciobanu L, Piciu A, Lucaciu O, Campian RS, Taulescu M, Bran S Abstract Proton pump inhibitors (PPIs) have become known for the treatment of gastric-acid related disorders. Similar to any other drugs, PPIs have possible adverse reactions, being associated with bone fractures, infections, kidney disease, mineral deficiency, dementia and pneumonia. Multiple analyses have stated that PPIs therapy may affect bone regeneration and osseointegration process, causing an increased risk of bone fracture, deterioration of bone metabolism and impaired bone healing. In this review, we emphasized the ...
Source: Drug Metabolism Reviews - May 7, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

The pathogenic microbial flora and its antibiotic susceptibility pattern in odontogenic infections.
Authors: Tent PA, Juncar RI, Onisor F, Bran S, Haranguș A, Juncar M Abstract Suppurative head and neck infections of odontogenic origin are the most frequent type of head and neck infections. According to the literature, 7-10% of all antibiotics are currently prescribed for their treatment. Since penicillin was invented, the overall antibiotic sensitivity and resistance pattern of the isolated pathogenic microflora has continuously changed. The response of microorganisms to antibiotics and the development of resistance to their action is a purely evolutive process characterized by genetic mutations, acquisition of...
Source: Drug Metabolism Reviews - April 20, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Mycotoxin patulin in food matrices: occurrence and its biological degradation strategies.
Authors: Sajid M, Mehmood S, Yuan Y, Yue T Abstract Patulin is a mycotoxin produced by a number of filamentous fungal species. It is a polyketide secondary metabolite which can gravely cause human health problems and food safety issues. This review deals with the occurrence of patulin in major food commodities from 2008 to date, including historical aspects, source, toxicity, and its regulatory limits. Most importantly, an overview of the recent research progress about the biodegradation strategies for contaminated food matrices is provided. The physical and chemical approaches have some drawbacks such as safety is...
Source: Drug Metabolism Reviews - March 14, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Graphene Nano-ribbon Based high potential and Efficiency for DNA, Cancer therapy and drug delivery applications.
Authors: Mousavi SM, Soroshni S, Hashemi SA, Babapoor A, Ghasemi Y, Mohammad Amani A Abstract At this article, graphene oxide Nano ribbons (GONRs) and its high potential for using in medical fields have been reviewed. Recently, Graphene Nano ribbons (GNRs) has been a field of interest in biological methods and disease treatment such as drug delivery, DNA applications, and photothermal cancer therapies. GNRs demonstrate more efficient properties rather than other graphene-based Nanomaterials due to their larger surface area. These novel properties made them into a remarkable substitute material for biological fields...
Source: Drug Metabolism Reviews - February 22, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Applications of graphene oxide in case of nanomedicines and nanocarriers for biomolecules: review study.
Authors: Mousavi SM, Hashemi SA, Ghasemi Y, Amani AM, Babapoor A, Arjmand O Abstract 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 g...
Source: Drug Metabolism Reviews - February 12, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Human cytochrome P450 enzymes 5-51 as targets of drugs and natural and environmental compounds: mechanisms, induction, and inhibition - toxic effects and benefits.
Authors: Rendic SP, Peter Guengerich F Abstract 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. We update an...
Source: Drug Metabolism Reviews - February 7, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Singularities of nevirapine metabolism: from sex-dependent differences to of idiosyncratic toxicity.
Authors: Marinho AT, Miranda JP, Caixas U, Charneira C, Gonçalves-Dias C, Marques MM, Monteiro EC, Antunes AMM, Pereira SA Abstract 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 ...
Source: Drug Metabolism Reviews - February 5, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Cannabinoids and Bone Regeneration.
Authors: Apostu D, Lucaciu O, Mester A, Benea H, Oltean-Dan D, Onisor F, Baciut M, Bran S Abstract 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...
Source: Drug Metabolism Reviews - February 1, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Novel insights into the pharmacometabonomics of first-line tuberculosis drugs relating to metabolism, mechanism of action and drug-resistance.
Authors: du Preez I, Loots DT Abstract 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...
Source: Drug Metabolism Reviews - December 20, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Aldehyde toxicity and metabolism: The role of aldehyde dehydrogenases in detoxification, drug resistance and carcinogenesis.
Authors: Laskar AA, Younus H Abstract 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). These enzyme systems maintain a low level of aldehydes in the body...
Source: Drug Metabolism Reviews - December 7, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

The engagement of brain cytochrome P450 in the metabolism of endogenous neuroactive substrates: a possible role in mental disorders.
Authors: Haduch A, Daniel WA Abstract 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 a...
Source: Drug Metabolism Reviews - December 7, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Regulation of brain drug metabolizing enzymes and transporters by nuclear receptors.
Authors: Xu D, Huang S, Wang H, Xie W Abstract 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 met...
Source: Drug Metabolism Reviews - December 7, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Clinical pharmacokinetics of drugs in cardiopulmonary associated cachexia without hepatorenal pathology: a systematic review.
Authors: Khan S, Shahzadi A Abstract 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 (ClinicalTrials.gov), encompassing the period between 2000 and 2017, was conducted in accordance to PRISMA guidelines. Seven st...
Source: Drug Metabolism Reviews - November 20, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Mechanistic investigation of resistance via drug inactivating enzymes in Mycobacterium tuberculosis.
Authors: Kashyap A, Singh PK, Silakari O Abstract 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 ta...
Source: Drug Metabolism Reviews - October 24, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Subcellular drug distribution: mechanisms and roles in drug efficacy, toxicity, resistance, and targeted delivery.
Authors: Li Q, Zhou T, Wu F, Li N, Wang R, Zhao Q, Ma YM, Zhang JQ, Ma BL Abstract 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-bind...
Source: Drug Metabolism Reviews - October 3, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Gut microbiota modulates drug pharmacokinetics.
Authors: Zhang J, Zhang J, Wang R Abstract 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...
Source: Drug Metabolism Reviews - September 21, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Alterations of drug-metabolizing enzymes and transporters under diabetic conditions: what is the potential clinical significance?
Authors: Chen F, Li DY, Zhang B, Sun JY, Sun F, Ji X, Qiu JC, Parker RB, Laizure SC, Xu J Abstract 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, pha...
Source: Drug Metabolism Reviews - September 19, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

The mesentery: an ADME perspective on a 'new' organ.
Authors: Argikar AA, Argikar UA Abstract 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 en...
Source: Drug Metabolism Reviews - July 18, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Insights into the intestinal bacterial metabolism of flavonoids and the bioactivities of their microbe-derived ring cleavage metabolites.
Authors: Feng X, Li Y, Brobbey Oppong M, Qiu F Abstract 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 metaboli...
Source: Drug Metabolism Reviews - July 18, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Biotransformation and bioactivation reactions - 2017 literature highlights *.
Authors: Khojasteh SC, Miller GP, Mitra K, Rietjens IMCM Abstract 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 t...
Source: Drug Metabolism Reviews - July 1, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

The synthetic cathinone α-pyrrolidinovalerophenone (α-PVP): pharmacokinetic and pharmacodynamic clinical and forensic aspects.
The synthetic cathinone α-pyrrolidinovalerophenone (α-PVP): pharmacokinetic and pharmacodynamic clinical and forensic aspects. Drug Metab Rev. 2018 Mar 14;:1-15 Authors: Nóbrega L, Dinis-Oliveira RJ Abstract 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 toxicokinet...
Source: Drug Metabolism Reviews - March 21, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Effects of 5-Aza-2'-deoxycytidine (decitabine) on gene expression.
Authors: Seelan RS, Mukhopadhyay P, Pisano MM, Greene RM Abstract 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...
Source: Drug Metabolism Reviews - February 21, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Cytochrome P450 in the central nervous system as a therapeutic target in neurodegenerative diseases.
Authors: Navarro-Mabarak C, Camacho-Carranza R, Espinosa-Aguirre JJ Abstract 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 metaboliz...
Source: Drug Metabolism Reviews - February 18, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Difference and alteration in pharmacokinetic and metabolic characteristics of low-solubility natural medicines.
Authors: Yan S, Liu Y, Feng J, Zhao H, Yu Z, Zhao J, Li Y, Zhang J Abstract 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 al...
Source: Drug Metabolism Reviews - February 4, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Targeting the endocannabinoid system as a potential anticancer approach.
Authors: Schwarz R, Ramer R, Hinz B Abstract 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 whe...
Source: Drug Metabolism Reviews - February 4, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Towards a better understanding of the cannabinoid-related orphan receptors GPR3, GPR6, and GPR12.
Authors: Morales P, Isawi I, Reggio PH Abstract 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 thi...
Source: Drug Metabolism Reviews - February 4, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Pro-psychotic effects of synthetic cannabinoids: interactions with central dopamine, serotonin, and glutamate systems.
Authors: Fantegrossi WE, Wilson CD, Berquist MD Abstract 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 neurotransm...
Source: Drug Metabolism Reviews - February 2, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research