Biotransformation of arsenic trioxide by AS3MT favors eradication of acute promyelocytic leukemia: revealing the hidden facts.
Authors: Maimaitiyiming Y, Zhu HH, Yang C, Naranmandura H Abstract Arsenic trioxide (ATO) is one of the most effective drugs for treatment of acute promyelocytic leukemia (APL). It could specifically target the PML/RARα fusion oncoprotein stability and induces APL cell differentiation as well as apoptosis. Although many studies have been conducted to document the anticancer effects and mechanism of ATO, there is little information about the association between biotransformation of ATO to active arsenic metabolites and APL therapy. Generally, ATO can be rapidly converted into trivalent methylated metabolites b...
Source: Drug Metabolism Reviews - July 18, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Mechanistic studies on the drug metabolism and toxicity originating from cytochromes P450.
Authors: Jaladanki CK, Gahlawat A, Rathod G, Sandhu H, Jahan K, Bharatam PV Abstract Cytochromes P450 are oxidizing enzymes; a few families of cytochromes P450 are implicated in drug metabolism. These enzymatic reactions involve many processes including (i) prodrug to drug conversion, (ii) easy excretion of drug, (iii) generation of reactive metabolites, many of which cause toxicity. In this review, the fundamental biochemical mechanisms associated with the conversion of drugs into the useful or toxic metabolites have been discussed. The mechanisms can be established with the help of many experimental methods like ...
Source: Drug Metabolism Reviews - July 11, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Novel advances in biotransformation and bioactivation research-2019 year in review.
Authors: Khojasteh SC, Driscoll JP, Jackson KD, Miller GP, Mitra K, Rietjens IMCM, Zhang D Abstract Biotransformation is one of the main mechanisms used by the body to eliminate drugs. As drug molecules become more complicated, the involvement of drug metabolizing enzymes increases beyond those that are typically studied, such as the cytochrome P450 enzymes. In this review, we try to capture the many outstanding articles that were published in the past year in the field of biotransformation (see Table 1). We have divided the articles into two categories of (1) metabolites and drug metabolizing enzymes, and (2) bioa...
Source: Drug Metabolism Reviews - July 11, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Towards human ex vivo organ perfusion models to elucidate drug pharmacokinetics in health and disease.
Authors: Stevens LJ, Donkers JM, Dubbeld J, Vaes WHJ, Knibbe CAJ, Alwayn IPJ, van de Steeg E Abstract To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions of ADME profiles earlier in the drug development process are very valuable. Good prediction of intestinal absorption and renal and biliary excretion remain especially diffi...
Source: Drug Metabolism Reviews - June 21, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

The broad-spectrum antiviral recommendations for drug discovery against COVID-19.
Authors: Hazafa A, Ur-Rahman K, Haq IU, Jahan N, Mumtaz M, Farman M, Naeem H, Abbas F, Naeem M, Sadiqa S, Bano S Abstract Despite to outbreaks of highly pathogenic beta and alpha coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus, the newly emerged 2019 coronavirus (COVID-19) is considered as a lethal zoonotic virus due to its deadly respiratory syndrome and high mortality rate among the human. Globally, more than 3,517,345 cases have been confirmed with 243,401 deaths due to Acute Respiratory Distress Synd...
Source: Drug Metabolism Reviews - June 18, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Advances in the study of drug metabolism - symposium report of the 12th Meeting of the International Society for the Study of Xenobiotics (ISSX).
Authors: Russell LE, Schleiff MA, Gonzalez E, Bart AG, Broccatelli F, Hartman JH, Humphreys WG, Lauschke VM, Martin I, Nwabufo C, Prasad B, Scott EE, Segall M, Takahashi R, Taub ME, Sodhi JK Abstract The 12th International Society for the Study of Xenobiotics (ISSX) meeting, held in Portland, OR, USA from July 28 to 31, 2019, was attended by diverse members of the pharmaceutical sciences community. The ISSX New Investigators Group provides learning and professional growth opportunities for student and early career members of ISSX. To share meeting content with those who were unable to attend, the ISSX New Investiga...
Source: Drug Metabolism Reviews - May 29, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Inhibition of CYP2C9 by natural products: insight into the potential risk of herb-drug interactions.
Authors: Wang K, Gao Q, Zhang T, Rao J, Ding L, Qiu F Abstract Due to the rapidly increasing global interest in the use of herbs, phytomedicines and other natural products as medical or complementary remedies, concerns about the clinical medication safety have drawn much attention worldwide. Particularly, many natural ingredients exhibit inhibitory effects on cytochrome P450 (CYP) enzymes, which are the most important Phase I metabolism enzymes in liver. CYP2C9 is one of the most abundant CYP enzymes and responsible for the metabolism of over 15% clinical drugs, including oral sulfonylurea hypoglycemics, nonsteroid...
Source: Drug Metabolism Reviews - May 16, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Nano-hydroxyapatite use in dentistry: a systematic review.
Authors: Bordea IR, Candrea S, Alexescu GT, Bran S, Băciuț M, Băciuț G, Lucaciu O, Dinu CM, Todea DA Abstract Nano-hydroxyapatite (nano-HA) is a material with multiple uses due to its biocompatibility and its resemblance to the nonorganic bone structure. It is used in various dental domains such as implantology, surgery, periodontology, esthetics and prevention. The aim of this study is to provide a wide understanding of nano-HA and to promote treatments based on nanomaterials in dentistry. A search in two data bases, Scopus, and PubMED, was conducted over a 5 years period. We chose a 5 years peri...
Source: Drug Metabolism Reviews - May 13, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Pharmacokinetics and pharmacodynamics of dextromethorphan: clinical and forensic aspects.
Authors: Silva AR, Dinis-Oliveira RJ Abstract Dextromethorphan (DXM) is a safe and effective antitussive agent present in several over the counter cough and cold medications. At higher doses, it causes psychoactive effects, making it appealing for abuse. In this work, the pharmacokinetics and pharmacodynamics of DXM with clinical and forensic relevance were extensively reviewed. DXM and related known metabolizing enzymes and metabolites were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period. Major metabolic pathways include sequential O-demethylation and N-demethylation o...
Source: Drug Metabolism Reviews - May 13, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Transcriptional regulation of CYP3A4 by nuclear receptors in human hepatocytes under hypoxia.
Authors: Yuan X, Lu H, Zhao A, Ding Y, Min Q, Wang R Abstract The human hepatic cytochrome P-450 3A4 (CYP3A4), recognized as a multifunctional enzyme, has a wide range of substrates including commonly used drugs. Previous investigations demonstrated that the expression of CYP3A4 in human hepatocytes could be regulated by some nuclear receptors (NRs) at transcriptional level under diverse situations. The significance of oxygen on CYP3A4-mediated metabolism seems notable while the regulatory mode of CYP3A4 in the particular case still remains elusive. Recently, striking evidence has emerged that both CYP3A4 and its r...
Source: Drug Metabolism Reviews - April 11, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Gold nanostars-diagnosis, bioimaging and biomedical applications.
Authors: Mousavi SM, Zarei M, Hashemi SA, Ramakrishna S, Chiang WH, Lai CW, Gholami A Abstract Gold Nanostars (GNS) have attracted tremendous attention toward themselves owing to their multi-branched structure and unique properties. These state of the art metallic nanoparticles possess intrinsic features like remarkable optical properties and exceptional physiochemical activities. These star-shaped gold nanoparticles can predominantly be utilized in biosensing, photothermal therapy, imaging, surface-enhanced Raman spectroscopy and target drug delivery applications due to their low toxicity and extraordinary optical...
Source: Drug Metabolism Reviews - March 10, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Lipid-based nanoformulations in the treatment of neurological disorders.
Authors: Pottoo FH, Sharma S, Javed MN, Barkat MA, Harshita, Alam MS, Naim MJ, Alam MO, Ansari MA, Barreto GE, Ashraf GM Abstract The neurological disorders affect millions of people worldwide, and are bracketed as the foremost basis of disability-adjusted life years (DALYs). The treatment options are symptomatic and often the movement of drugs is restricted by a specialized network of endothelial cell layers (adjoined by tight cell-to-cell junction proteins; occludin, claudins, and junctional adhesion molecules), pericytes and astroglial foot processes. In recent years, advances in nanomedicine have led to therapi...
Source: Drug Metabolism Reviews - March 3, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

The metabolic effect of gut microbiota on drugs.
Authors: Xie Y, Hu F, Xiang D, Lu H, Li W, Zhao A, Huang L, Wang R Abstract There are more than 1000 species of microbes reside in the human gut, umbering∼1014 microbes. As the invisible organ of human beings, gut microbiota can usually participate in drug metabolism by producing specific enzymes, such as reductase and hydrolytic enzyme, thus affecting the efficacy, toxicity, and bioavailability of drugs. At least 30 commercially available drugs have been shown to be substrates of gut microbes-derived enzymes, and an increasing number of drugs may have the potential to contact with the distal gut with the help ...
Source: Drug Metabolism Reviews - March 3, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Current trends in chemical modifications of magnetic nanoparticles for targeted drug delivery in cancer chemotherapy.
Authors: Gholami A, Mousavi SM, Hashemi SA, Ghasemi Y, Chiang WH, Parvin N Abstract Nowadays, magnetic nanoparticles (MNPs) have been rapidly investigated and attracted worldwide attention due to their great potential as mediators of heat for treating hyperthermia and their possibility to deliver drugs at specific locations, which can thereby limit systematic effects. Cancer therapy via MNPs proposes novel properties rather than normal methods such as almost zero side effects and a high-efficiency rate of effectiveness. The key aim of targeted drug delivery is to reduce side effects of the main cancer treatment tha...
Source: Drug Metabolism Reviews - February 24, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Entering the era of computationally driven drug development.
Authors: Maharao N, Antontsev V, Wright M, Varshney J Abstract Historically, failure rates in drug development are high; increased sophistication and investment throughout the process has shifted the reasons for attrition, but the overall success rates have remained stubbornly and consistently low. Only 8% of new entities entering clinical testing gain regulatory approval, indicating that significant obstacles still exist for efficient therapeutic development. The continued high failure rate can be partially attributed to the inability to link drug exposure with the magnitude of observed safety and efficacy-related...
Source: Drug Metabolism Reviews - February 24, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Metabolism of bioconjugate therapeutics: why, when, and how?
This article provides a comprehensive overview of linker cleavage pathways and catabolism/metabolism of antibody-drug conjugates, glycoconjugates, polymer-drug conjugates, lipid-drug conjugates, folate-targeted small molecule-drug conjugates, and drug-drug conjugates. PMID: 32045530 [PubMed - as supplied by publisher] (Source: Drug Metabolism Reviews)
Source: Drug Metabolism Reviews - February 12, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Understanding variability in the pharmacokinetics of atypical antipsychotics - focus on clozapine, olanzapine and aripiprazole population models.
Authors: Jovanović M, Vučićević K, Miljković B Abstract Antipsychotic medicines are widely used for the management of psychotic symptoms regardless of the underlying diagnosis. Most atypical antipsychotics undergo extensive metabolism prior to excretion. Various factors may influence their pharmacokinetics, particularly elimination, leading to highly variable drug concentrations between individual patients following the same dosing regimen. Population pharmacokinetic approach, based on nonlinear mixed effects modeling, is a useful tool to identify covariates explaining pharmacokinetic variability, as well as t...
Source: Drug Metabolism Reviews - February 6, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Insights into gastrointestinal microbiota-generated ginsenoside metabolites and their bioactivities.
Authors: Yang L, Zou H, Gao Y, Luo J, Xie X, Meng W, Zhou H, Tan Z Abstract The gastrointestinal microbiota and host co-evolve into a complex 'super-organism,' and this relationship plays a vital role in many physiological processes, such as drug metabolism. Ginseng is an important medicinal resource and the main ingredients are ginsenosides, which are less polar, difficult to absorb, and have low bioavailability. However, studies have shown that the biological activity of ginsenosides such as compound K (CK), ginsenoside Rg3 (Rg3), ginsenoside Rh2 (Rh2), 20(S)-protopanaxatriol (20(S)-PPT), and 20(S)-protopanaxadio...
Source: Drug Metabolism Reviews - January 29, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Toward a better understanding of metabolic and pharmacokinetic characteristics of low-solubility, low-permeability natural medicines.
Authors: Yang J, Li K, He D, Gu J, Xu J, Xie J, Zhang M, Liu Y, Tan Q, Zhang J Abstract Today, it is very challenging to develop new active pharmaceutical ingredients. Developing good preparations of well-recognized natural medicines is certainly a practical and economic strategy. Low-solubility, low-permeability natural medicines (LLNMs) possess valuable advantages such as effectiveness, relative low cost and low toxicity, which is shown by the presence of popular products on the market. Understanding the in vivo metabolic and pharmacokinetic characteristics of LLNMs contributes to overcoming their associated...
Source: Drug Metabolism Reviews - January 29, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Adverse pharmacokinetic interactions between illicit substances and clinical drugs.
Authors: Abbott KL, Flannery PC, Gill KS, Boothe DM, Dhanasekaran M, Mani S, Pondugula SR Abstract Adverse pharmacokinetic interactions between illicit substances and clinical drugs are of a significant health concern. Illicit substances are taken by healthy individuals as well as by patients with medical conditions such as mental illnesses, acquired immunodeficiency syndrome, diabetes mellitus and cancer. Many individuals that use illicit substances simultaneously take clinical drugs meant for targeted treatment. This concomitant usage can lead to life-threatening pharmacokinetic interactions between illicit subst...
Source: Drug Metabolism Reviews - December 14, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

Introduction of magnetic and supermagnetic nanoparticles in new approach of targeting drug delivery and cancer therapy application.
Authors: Avval ZM, Malekpour L, Raeisi F, Babapoor A, Mousavi SM, Hashemi SA, Salari M Abstract In this article, the recent applications of different types of magnetic nanoparticles such as α-Fe2O3 (hematite), γ-Fe2O3 (maghemite), Fe3O4 (magnetite), hexagonal (MFe12O19), garnet (M3Fe5O12) and spinel (MFe2O4), where M represents one or more bivalent transition metals (Mn, Fe, Co, Ni, Ba, Sr, Cu, and Zn), and different materials for coating the surface of magnetic nanoparticles like poly lactic acid (PLA), doxorubicin hydrophobic (DOX-HCL), paclitaxel (PTX), EPPT-FITC, oleic acid, tannin, 3-Aminopropyltri...
Source: Drug Metabolism Reviews - December 14, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Rev Source Type: research

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