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Expert Opinion on Drug Metabolism & Toxicology

Sri Riyati Sugiarto, Timothy M E Davis, Sam Salman
Artemisinin-based combination therapy (ACT) is used extensively as first-line treatment for uncomplicated falciparum malaria. There has been no rigorous assessment of the potential for racial/ethnic differences in the pharmacokinetic properties of ACTs that might influence their pharmacokinetic properties. Areas covered: A comprehensive literature search was performed that identified 72 publications in which the geographical origin of the patients could be ascertained and the key pharmacokinetic parameters maximum drug concentration (Cmax), area under the plasma concentration-time curve (AUC) and elimination half-life (t½β) were available for one or more of the five WHO-recommended ACTs (artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine, dihydroartemisinin-piperaquine and artesunate-sulfadoxine-pyrimethamine)...
October 13, 2017: Expert Opinion on Drug Metabolism & Toxicology
Jarrett R Amsden, Paul O Gubbins
Introduction Triazole antifungal agents are prescribed to treat invasive fungal infections in neutropenic and non-neutropenic patients. These antifungal agents are substrates and inhibitors of cytochrome P450 (CYP). Genetic polymorphisms in CYP2C9, CYP2C19 and CYP3A5 can lead to large population-specific variations in drug efficacy and safety, optimal dosing, or contribute to drug interactions associated with this class. Areas covered This manuscript reviews the pharmacogenomics (i.e. the influence of genetics on drug disposition) of triazole antifungal agents related to their CYP-mediated metabolism and summarizes their implications on triazole efficacy, safety, and tolerability...
October 12, 2017: Expert Opinion on Drug Metabolism & Toxicology
M Neary, A Owen
Variations in the human genome sequence sometimes play an important role in pharmacokinetics and/or pharmacodynamics. Previous studies have demonstrated a high degree of variation both between and within different ethnic populations. Areas Covered: This review sought to summarise key SNPs in CYP2B6, CYP3A enzymes, CYP2C enzymes, UGT2 enzymes, ABCB1, ABCC2, SLCO1B1, NR1I2 and NR1I3 that have previously been associated with variability in antiretroviral pharmacokinetics. Additionally, the impact of ethnicity in these pharmacogenetics studies is discussed and variation in findings between different ethnic groups is reviewed...
October 10, 2017: Expert Opinion on Drug Metabolism & Toxicology
Maria Gabriella Matera, Barbara Rinaldi, Luigino Calzetta, Mario Cazzola
Pharmacogenetic and pharmacogenomic approaches are already utilized in some areas, such as oncology and cardiovascular disease, for selecting appropriate patients and/or establishing treatment and dosing guidelines. This is not true in asthma although many patients have different responses to drug treatment due to genetic factors. Areas covered: Several genetic factors that affect the pharmacotherapeutic responses to asthma medications, such as β2-AR agonists, corticosteroids, and leukotriene modifiers and could contribute to significant between-person variability in response are described...
October 10, 2017: Expert Opinion on Drug Metabolism & Toxicology
Saeed Alqahtani
Although significant progress has been made in high-throughput screening of absorption, distribution, metabolism and excretion, and toxicity (ADME-Tox) properties in drug discovery and development, in silico ADME-Tox prediction continues to play an important role in facilitating the appropriate selection of candidate drugs by pharmaceutical companies prior to expensive clinical trials. Areas covered: This review provides an overview of the available in silico models that have been used to predict the ADME-Tox properties of compounds...
October 9, 2017: Expert Opinion on Drug Metabolism & Toxicology
Matteo Bassetti, Davide Pecori, Piergiorgio Cojutti, Federico Pea
In the era of multi-drug resistant pathogens, the adequate treatment of skin and skin structure infections remains a challenge for clinicians. Delafloxacin, with its broad spectrum against Gram-positive, Gram-negative and anaerobic organisms, represents a new therapeutic option in this setting, especially when coverage of methicillin-resistant Staphylococcus aureus is required in the empirical or targeted approach. Areas covered: In this drug evaluation, the Authors have reviewed the pharmacokinetic and pharmacodynamic characteristics of delafloxacin...
October 9, 2017: Expert Opinion on Drug Metabolism & Toxicology
Tara Richardson, Matthew Macaluso
The goal of this paper is to provide a practical, clinically oriented review of lithium, a salt widely used to treat mania since the 1870s and formally approved as a mood stabilizer in 1970. Although lithium is still considered a first-line treatment for bipolar mania in most practice guidelines, its use may be overshadowed by newer psychotropic medications. Areas Covered: This paper addresses the historical use of lithium, modern indications for its use, guidelines for prescribing and monitoring continued lithium use, drug-drug interactions, and pharmacodynamics/pharmacokinetic properties...
October 2, 2017: Expert Opinion on Drug Metabolism & Toxicology
Francesco Panza, Madia Lozupone, Vincenzo Solfrizzi, Roberta Stallone, Antonello Bellomo, Antonio Greco, Antonio Daniele, Davide Seripa, Giancarlo Logroscino
No abstract text is available yet for this article.
September 5, 2017: Expert Opinion on Drug Metabolism & Toxicology
Amedeo F Capetti, Noemi Astuti, Dario Cattaneo, Giuliano Rizzardini
The search for simple, potent, metabolic-friendly and nucleoside/nucleotide sparing antiretroviral regimens has led clinical investigators to move steps towards dual therapies. Among these the association of rilpivirine and dolutegravir is emerging as a twin randomized clinical trial (SWORD1&2) and at least three observational cohort describe it as a safe and highly effective regimen for switch from other therapies Areas covered: We review the evidence supporting the use of dolutegravir plus rilpivirine for the treatment of HIV in virologically suppressed patients taking other antiretroviral regimens...
August 30, 2017: Expert Opinion on Drug Metabolism & Toxicology
Debra Luffer-Atlas, Aisar Atrakchi
No abstract text is available yet for this article.
August 11, 2017: Expert Opinion on Drug Metabolism & Toxicology
Marilisa Bove, Federica Fogacci, Arrigo F G Cicero
Cholesterol lowering treatment is mainly based on statins eventually associated to adjunctive drugs of different class such as ezetimibe. In the present review, we analysed the pharmacokinetics, efficacy and safety of ezetimibe + simvastatin drug association. Areas covered: The bio-equivalence of ezetimibe and simvastatin when co-administrated in separate tablets or combined in a single pill is well documented. Ezetimibe is absorbed in small intestine, reaching peak plasma concentrations in 4-12 h, with a plasma half-life of 22 h...
October 2017: Expert Opinion on Drug Metabolism & Toxicology
Hasan Turkez, Mehmet E Arslan, Ozlem Ozdemir
Genotoxicity and mutagenicity analyses have a significant role in the identification of hazard effects of therapeutic drugs, cosmetics, agrochemicals, industrial compounds, food additives, natural toxins and nanomaterials for regulatory purposes. To evaluate mutagenicity or genotoxicity, different in vitro and in vivo methodologies exert various genotoxicological endpoints such as point mutations, changes in number and structure of chromosomes. Areas covered: This review covered the basics of genotoxicity and in vitro/in vivo methods for determining of genetic damages...
October 2017: Expert Opinion on Drug Metabolism & Toxicology
Samaneh Soleymani, Roodabeh Bahramsoltani, Roja Rahimi, Mohammad Abdollahi
St. John's wort (SJW) is a common medicinal herb used for the treatment of mild to moderate depression. Hyperforin, one of the chief components of SJW, plays an important role in the induction of cytochrome P450 enzymes (CYP) and P-glycoprotein transporter (P-gp), and therefore, affects the pharmacokinetics of various drugs. There are several clinical studies demonstrating the interaction of SJW with the metabolism of conventional drugs which may cause life-threatening events. Areas covered: This review focuses on human studies that have evaluated pharmacokinetic alterations of conventional drugs in concomitant use with different SJW preparations...
October 2017: Expert Opinion on Drug Metabolism & Toxicology
Uni Wong, Raymond K Cross
Primary and secondary non-response to infliximab are common in patients with inflammatory bowel disease and remain a management challenge in clinical practice. Areas covered: This article describes the epidemiology, mechanisms and risk factors for primary and secondary nonresponse to infliximab in patients with inflammatory bowel disease. Data on proactive and reactive therapeutic drug monitoring are examined in this review. An algorithm for evaluation and management of non-response to infliximab is provided...
October 2017: Expert Opinion on Drug Metabolism & Toxicology
Osama Y Alshogran
Genetic variation in metabolizing enzymes contributes to variable drug response and disease risk. Aldo-keto reductase type 1C (AKR1C) comprises a sub-family of reductase enzymes that play critical roles in the biotransformation of various drug substrates and endogenous compounds such as steroids. Several single nucleotide polymorphisms have been reported among AKR1C encoding genes, which may affect the functional expression of the enzymes. Areas covered: This review highlights and comprehensively discusses previous pharmacogenetic reports that have examined genetic variations in AKR1C and their association with disease development, drug disposition, and therapeutic outcomes...
October 2017: Expert Opinion on Drug Metabolism & Toxicology
Maka S Hedrington, Stephen N Davis
Normal pregnancy development involves gradual decline in insulin sensitivity, which sometimes requires pharmacotherapy. Insulin is the drug of choice for gestational and pregestational diabetes. Metabolism of traditional insulins results in inadequate onset and duration of action and marked peak activity. These properties increase risk of excessive glucose excursions, which are especially undesirable during pregnancy. Insulin analogs have been emerging as a safer and more effective treatment of diabetes during pregnancy...
October 2017: Expert Opinion on Drug Metabolism & Toxicology
Eve-Irene Lepist, Adrian S Ray
Membrane transport proteins play a central role in regulating the disposition of endobiotics, dietary nutrients and environmental toxins. The inhibition of transporters by drugs has potential physiologic consequences. The full extent of the effect of drugs on the function of transporters is poorly understood because only a small subset of the hundreds of transporters expressed in humans - primarily those mediating the rate-determining step in the elimination of specific drugs - are assessed during clinical development...
October 2017: Expert Opinion on Drug Metabolism & Toxicology
Elliot Berinstein, Andrew Levy
Cardiovascular disease is still the leading cause of death worldwide. There are many environmental and genetic factors that play a role in the development of cardiovascular disease. The treatment of cardiovascular disease is beginning to move in the direction of personalized medicine by using biomarkers from the patient's genome to design more effective treatment plans. Pharmacogenomics have already uncovered many links between genetic variation and response of many different drugs. Areas covered: This article will focus on the main polymorphisms that impact the risk of adverse effects and response efficacy of statins, clopidogrel, aspirin, β-blockers, warfarin dalcetrapib and vitamin E...
September 2017: Expert Opinion on Drug Metabolism & Toxicology
Jeffry Adiwidjaja, Andrew J McLachlan, Alan V Boddy
Curcumin has been extensively studied for its anti-cancer properties. While a diverse array of in vitro and preclinical research support the prospect of curcumin use as an anti-cancer therapeutic, most human studies have failed to meet the intended clinical expectation. Poor systemic availability of orally-administered curcumin may account for this disparity. Areas covered: This descriptive review aims to concisely summarise available clinical studies investigating curcumin pharmacokinetics when administered in different formulations...
September 2017: Expert Opinion on Drug Metabolism & Toxicology
Matthew W Linakis, Kathleen M Job, Xiaoxi Liu, Scott C Collingwood, Heather A Pangburn, Darrin K Ott, Catherine M T Sherwin
When in flight, pilots of high performance aircraft experience conditions unique to their profession. Training flights, performed as often as several times a week, can expose these pilots to altitudes in excess of 15 km (~50,000 ft, with a cabin pressurized to an altitude of ~20,000 ft), and the maneuvers performed in flight can exacerbate the G-forces felt by the pilot. While the pilots specifically train to withstand these extreme conditions, the physiologic stress could very likely lead to differences in the disposition of chemicals in the body, and consequently, dangerously high exposures...
September 2017: Expert Opinion on Drug Metabolism & Toxicology
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