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Expert Opinion on Drug Metabolism & Toxicology

L E J Peeters, M P Kester, L Feyz, P M L A Van Den Bemt, B C P Koch, T Van Gelder, J Versmissen
Hypertension is an important risk factor for developing cardiovascular diseases. It is more prevalent in the elderly population. Recently updated American and European guidelines recommend treating every elderly patient with hypertension independent of age, starting with a low dose of antihypertensive drugs. However, little information is available on the optimal dosages of antihypertensive drugs to treat the elderly safely. Areas covered: Comorbidities, co-medication and frailty status can alter the clinical outcome of drug treatment and can cause adverse events in the elderly...
March 16, 2019: Expert Opinion on Drug Metabolism & Toxicology
Zsolt Safar, Emses Kis, Franciska Erdo, Joseph K Zolnerciks, Peter Krajcsi
ABCG2 has a broad substrate specificity and is one of the most important efflux proteins modulating pharmacokinetics of drugs, nutrients, and toxicokinetics of toxicants. ABCG2 is an important player in transporter-mediated drug-drug interactions (tDDI). Areas covered: The aims of the review are i) to cover transporter interaction profile of substrates and inhibitors that can be utilized to test interaction of drug candidates with ABCG2, ii) to highlight main characteristics of in vitro testing and iii) to describe the structural basis of the broad substrate specificity of the protein...
March 11, 2019: Expert Opinion on Drug Metabolism & Toxicology
Samaneh Nakhaee, Omid Mehrpour
No abstract text is available yet for this article.
March 8, 2019: Expert Opinion on Drug Metabolism & Toxicology
Alvaro Garcia-Ropero, Carlos G Santos-Gallego, Urooj M Zafar, Juan J Badimon
Cardiac metabolism represents a complex network of numerous pathways responsible for adequate supply of ATP to the incessant contractile apparatus. Impairments of such pathways are associated with myocardial dysfunction. The newest antidiabetic drugs, the SGLT2 inhibitors, have been demonstrated to reduce cardiovascular mortality and heart failure hospitalizations. The mechanisms underlying these benefits are still uncertain; however, they may play a decisive role in restoring energy efficiency to the damaged heart...
March 1, 2019: Expert Opinion on Drug Metabolism & Toxicology
Claudia Maria Hattinger, Maria Pia Patrizio, Silvia Luppi, Federica Magagnoli, Piero Picci, Massimo Serra
DNA damaging drugs are widely used for the chemotherapeutic treatment of high-grade osteosarcoma (HGOS). In HGOS patients, several germline polymorphisms have been reported to impact on the development of adverse toxic events related to DNA damaging drugs treatment. Some of these polymorphisms, when present in tumor cells, may also influence treatment response and prognosis of HGOS patients. Area covered. In this review, the authors have focused on pharmacogenetic markers (mainly germline polymorphisms) described in patients with HGOS, which have proved or indicated to be related to the susceptibility to adverse toxic reactions and/or to influence response to DNA damaging drugs...
March 1, 2019: Expert Opinion on Drug Metabolism & Toxicology
Anne Caroline S Barbosa, Ye Feng, Chaohui Yu, Min Huang, Wen Xie
Biotransformation is important in the metabolism of endobiotics and xenobiotics. This process comprises the activity of phase I and phase II enzymes. Estrogen sulfotransferase (SULT1E1 or EST) is a phase II conjugating enzyme that belongs to the family of cytosolic sulfotransferases. The expression of SULT1E1 can be detected in many tissues, including the liver. SULT1E1 catalyzes the transfer of a sulfate group from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to any available hydroxyl group in estrogenic molecules...
March 1, 2019: Expert Opinion on Drug Metabolism & Toxicology
Donatella Marazziti, Maria Teresa Avella, Lucia Basile, Federico Mucci, Liliana Dell'Osso
Although the treatment of obsessive-compulsive disorder (OCD), a common, chronic and disabling psychiatric condition, has significantly improved in the last decades, with the demonstration of the specific effectiveness of serotonin reuptake inhibitors (SRIs), a large proportion of patients still show high relapse rates. In addition, pharmacological treatments should be maintained for years, so that the clinicians should take into account the pharmacokinetic changes in the long-term, which may be responsible for dangerous side effects or interactions...
February 22, 2019: Expert Opinion on Drug Metabolism & Toxicology
Marc Rendell
Although premixed fixed ratio NPH insulin products are commonly used in type 2 diabetes patients, the advent of Glargine insulin which cannot be formulated together with a rapid acting insulin (basal-bolus) has largely eliminated premixed insulin from use in type 1 diabetes. Degludec insulin can be formulated together with Aspart insulin in a 70/30 fixed ratio product. We review the potential use of Degludec-Aspart in type 1 diabetes. Areas covered: A historical search of the development and use of premixed insulin preparations was performed relying on Pubmed, FDA, and European Union records...
February 21, 2019: Expert Opinion on Drug Metabolism & Toxicology
Chiari Lupi, Silvia Benemei, Simona Guerzoni, Lanfranco Pellesi, Andrea Negro
Recommended medications for the acute treatment of migraine encompass triptans, nonsteroidal anti-inflammatory drugs (NSAIDs), and analgesics. While it is true that triptans have been the first successful mechanism-driven treatment in the field, recently, new targets involved in migraine pathogenesis have emerged and new drug classes have been studied for migraine attack therapy. Areas covered: Pharmacodynamics and pharmacokinetics of the new acute treatments of migraine (i.e. ditans, gepants, and glutamate receptor antagonists), considering also marketed drugs in new formulations and administration routes...
February 4, 2019: Expert Opinion on Drug Metabolism & Toxicology
Dario Cattaneo, Amedeo Capetti, Giuliano Rizzardini
The GEMINI trials have recently shown that a 2-drug regimen of dolutegravir plus lamivudine was non-inferior to a three-drug regimen in HIV-infected naïve patients. Accordingly, it is important that physicians be aware and confident about the drug-drug interactions (DDIs) involving dolutegravir, lamivudine and other medications. Areas covered: Here, we firstly update the available information on the pharmacokinetic features of dolutegravir and lamivudine; subsequently, the articles mainly deals with the predictable drug-drug interactions (DDIs) for both antiretroviral drugs, attempting to underline their clinical implications...
January 31, 2019: Expert Opinion on Drug Metabolism & Toxicology
Alberto Verrotti, Giulia Iapadre, Giulia Di Donato, Ludovica Di Francesco, Luca Zagaroli, Sara Matricardi, Vincenzo Belcastro, Maria Laura Iezzi
Epilepsy is a chronic and debilitating neurological disease, with a peak of incidence in the first years of life. Today, the vast armamentarium of antiepileptic drugs (AEDs) available make even more challenging to select the most appropriate AED and establish the most effective dosing regimen. In fact, AEDs pharmacokinetics is under the influence of important age-related factors which cannot be ignored. Areas to be covered: Physiological changes occurring during development age (different body composition, immature metabolic patterns, reduced renal activity), can significantly modify the pharmacokinetic profile of AEDs (adsorption, volume of distribution, half-life, clearance), leading to an altered treatment response...
January 28, 2019: Expert Opinion on Drug Metabolism & Toxicology
Joseph J Jennings, Rohan Mandaliya, Ahmad Nakshabandi, James H Lewis
Immune checkpoint inhibitors (ICIs) block cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/PD ligand 1 (PD-L1) receptors that control antitumor activities of lymphocytes. While highly efficacious, these drugs have been associated with several immune-related adverse events (irAEs) due to the disruption of self-tolerance. Immune-mediated hepatitis (IMH) usually presents as mild elevations of liver enzymes though it can rarely be associated with life-threatening hepatic injury...
January 24, 2019: Expert Opinion on Drug Metabolism & Toxicology
Patrick Tarnow, Tewes Tralau, Andreas Luch
Estrogen receptors (ERs) and the arylhydrocarbon receptor (AHR) are ligand activated transcription factors that regulate the expression of genes involved in many physiological processes. With both receptors binding a broad range of natural and anthropogenic ligands, they are molecular targets for many substances, raising concerns for possible health effects. Areas Covered: This review shall give a brief overview on the physiological functions of both receptors including their underlying molecular mechanisms...
January 15, 2019: Expert Opinion on Drug Metabolism & Toxicology
Dubravka Vejnović, Vera Milić, Branka Popović, Tatjana Damnjanović, Nela Maksimović, Vera Bunjevački, Maja Krajinović, Ivana Novaković, Nemanja Damjanov, Biljana Jekić
BACKGROUND: Methotrexate, a folate analogue, is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis. However, high interindividual differences in drug response are present among RA patients. RESEARCH DESIGN AND METHODS: In a group of 234 RA patients treated with MTX we investigated whether rs1650697 polymorphism in DHFR gene may have impact on MTX efficacy and/or adverse drug effects (ADEs). Relative DAS28 values (rDAS28) were used for MTX therapy estimation and all adverse drug events were recorded...
December 24, 2018: Expert Opinion on Drug Metabolism & Toxicology
Liping Wang, Rongjin Sun, Qisong Zhang, Qing Luo, Sijing Zeng, Xiaoyan Li, Xia Gong, Yuhuan Li, Linlin Lu, Ming Hu, Zhongqiu Liu
Polyphenols, which are widely distributed in plants and the human diets, are known to have numerous biological activities. However, the low bioavailability of polyphenols is mediated by coupled metabolic pathways. Areas covered: The key role of the interplay between drug metabolic enzymes (DMEs) and efflux transporters (ETs), nuclear receptors (NRs), and intestinal microflora in the disposition of polyphenols is summarized. Expert opinion: ETs are shown to act as a 'revolving door', facilitating and/or controlling cellular polyphenol glucuronide/sulfate excretion...
December 24, 2018: Expert Opinion on Drug Metabolism & Toxicology
Na Li, Ting Zhou, Fei Wu, Rui Wang, Qing Zhao, Ji-Quan Zhang, Bai-Can Yang, Bing-Liang Ma
Glycyrrhizae Radix et Rhizoma (Gancao in Chinese) is the most frequently used traditional Chinese medicine (TCM) owing to its various pharmacological effects and, more importantly, the synergistic effects that enhance the efficacy and reduce the toxicity of other TCMs. Areas covered: We reviewed publications, predominantly between 1990 and 2018, that examined pharmacokinetic interactions between Gancao and other TCMs, or the bioactive constituents of these TCMs. This review focuses on the underlying mechanisms and the components responsible for the pharmacokinetic modulation by Gancao...
December 24, 2018: Expert Opinion on Drug Metabolism & Toxicology
Tan V Le, Peter Tsambarlis, Wayne J G Hellstrom
Erectile dysfunction (ED) is one of the most common complaints encountered by the practicing urologist, particularly when treating older men. The last 20 years have represented a pivotal time in the treatment of ED. Areas covered: Several pharmacologic agents have been approved by regulatory agencies, including phosphodiesterase type 5 (PDE5) inhibitors, intraurethral suppositories, and vasoactive injectable agents. This review will focus on the pharmacodynamic properties of these agents and the clinical consequences of those properties...
December 22, 2018: Expert Opinion on Drug Metabolism & Toxicology
Marie Robert, Jean-Sébastien Frenel, Emmanuelle Bourbouloux, Dominique Berton Rigaud, Anne Patsouris, Paule Augereau, Carole Gourmelon, Mario Campone
The combination of cyclin-dependent kinases 4 and 6 (CDK 4 and 6) inhibitors with endocrine therapy represents a new standard of care for endocrine-receptor positive metastatic breast cancer. Currently, three compounds are approved. Abemaciclib is the latest CDK4/6 inhibitor approved by the US Food and Drug Administration in view of the results of the MONARCH1 and 2 trials. Area covered: In this article, we review the preclinical and clinical development of abemaciclib in advanced breast cancer, describing current therapeutic indications and open questions...
December 21, 2018: Expert Opinion on Drug Metabolism & Toxicology
Stefano de Biase, Gian Luigi Gigli, Annacarmen Nilo, Giorgia Romano, Mariarosaria Valente
Medical therapy is the mainstay of management of epilepsy. Despite the increasing number of available antiepileptic drugs (AEDs), approximately one-third of epileptic patients do not have adequate control of seizures. There is still need for the development of new AEDs with enhanced effectiveness and tolerability. Areas covered: The present manuscript is based on an Internet and PubMed search (January 2005 to August 2018). It is focused on pharmacokinetic and clinical data of perampanel (PER) for the treatment of epilepsy...
December 21, 2018: Expert Opinion on Drug Metabolism & Toxicology
Vojo Deretic, Graham S Timmins
Major unmet needs remain for improved antibiotic treatment in lung infections. While development of new antibiotics is needed to overcome resistance, other approaches to optimize therapy using existing agents are also attractive. Ambroxol induces lung autophagy at human-relevant doses and improves lung levels of several approved antibiotics. Areas covered: This review discusses preclinical and clinical studies of the effects of ambroxol (and its prodrug precursor bromhexine) co-treatment upon levels of antibiotics in lung tissue, sputum, and bronchoalveolar lavage fluid...
March 2019: Expert Opinion on Drug Metabolism & Toxicology
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