Abstract:
IMPORTANCE OF THE FIELD:many promising targeted agents and combination therapies are being investigated for brain cancer. However, the results from recent clinical trials have been disappointing. A better understanding of the disposition of drug in the brain early in drug development would facilitate appropriate channeling of new drugs into brain cancer clinical trials. AREAS COVERED IN THIS REVIEW:barriers to successful drug activity against brain cancer and issues affecting intratumoral drug concentrations are reviewed. The use of the microdialysis technique for extracellular fluid (ECF) sampling and its application to drug distribution studies in brain are reviewed using published literature from 1995 to the present. The benefits and limitations of microdialysis for performing neuorpharmacokinetic (nPK) and neuropharmacodynamic (nPD) studies are discussed. WHAT THE READER WILL GAIN:the reader will gain an appreciation of the challenges involved in identifying agents likely to have efficacy in brain cancer, an understanding of the general principles of microdialysis, and the power and limitations of using this technique in early drug development for brain cancer therapies. TAKE HOME MESSAGE:a major factor preventing efficacy of anti-brain cancer drugs is limited access to tumor. Intracerebral microdialysis allows sampling of drug in the brain ECF. The resulting nPK/nPD data can aid in the rational selection of drugs for investigation in brain tumor clinical trials.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Blakeley J,Portnow Jdoi
10.1517/17425255.2010.523420subject
Has Abstractpub_date
2010-12-01 00:00:00pages
1477-91issue
12eissn
1742-5255issn
1744-7607journal_volume
6pub_type
杂志文章,评审abstract:IMPORTANCE OF THE FIELD:genetic and pharmacologically-driven variations in common mechanisms involved in the disposition of antidepressant medications may contribute to variable interpatient response. This review describes the pharmacological properties underlying the safety and efficacy of desvenlafaxine, a second-gen...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2010.535810
更新日期:2010-12-01 00:00:00
abstract:INTRODUCTION:Invasive fungal infections remain a leading cause of infectious morbidity and mortality in immunocompromised patients. There are relatively few effective antifungal agents, and currently available agents all have significant limitations. Isavuconazole is a novel second-generation triazole with broad-spectr...
journal_title:Expert opinion on drug metabolism & toxicology
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doi:10.1517/17425255.2012.683859
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abstract:INTRODUCTION:Lenalidomide is an oral immunomodulatory drug, which was recently introduced for the treatment of multiple myeloma (MM). It has been used for the treatment of newly diagnosed and relapsed MM patients, as both maintenance and preventive therapy. Available data show a progression-free survival and overall su...
journal_title:Expert opinion on drug metabolism & toxicology
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doi:10.1517/17425255.2012.712685
更新日期:2012-09-01 00:00:00
abstract::Acetaminophen (APAP) hepatotoxicity is currently the single most important cause of acute liver failure in the US, and is associated with a significant number of deaths. The toxic response to APAP is triggered by a highly reactive metabolite N-acetyl-p-benzoquinone-imine. Following the hepatocellular initiation events...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.4.493
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abstract:INTRODUCTION:The elucidation of the toxicological mechanisms of herbal medicines is becoming more and more important with the increasing application of herbal medicines, for treatment of various diseases and the promotion of health. Furthermore, it is widely recognized that as herbal components undergo bioactivation, t...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.586335
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:The activity of various CYP isoforms is critical for maintaining the clinical effectiveness of many medications. Therefore, determining the sex-dependent activity of clinically relevant CYP families is highly important for optimal therapeutic effectiveness. OBJECTIVE:This review examined the sex-dependent a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.4.413
更新日期:2008-04-01 00:00:00
abstract:INTRODUCTION:The N-acetylation polymorphism has been the subject of comprehensive reviews describing the role of arylamine N-acetyltransferase 2 (NAT2) in the metabolism of numerous aromatic amine and hydrazine drugs. AREAS COVERED:We describe and review data that more clearly defines the effects of NAT2 haplotypes an...
journal_title:Expert opinion on drug metabolism & toxicology
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更新日期:2021-01-01 00:00:00
abstract:INTRODUCTION:The key feature of the newborn is its fast age-dependent maturation, resulting in extensive variability in pharmacokinetics and -dynamics, further aggravated by newly emerging covariates like treatment modalities, environmental issues or pharmacogenetics. This makes clinical research in neonates relevant a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1046433
更新日期:2015-07-01 00:00:00
abstract:INTRODUCTION:There are profound changes that take place in drug metabolism enzymes during fetal and postnatal development. These changes may significantly impact drug therapy in children. AREAS COVERED:A combination of focused and comprehensive literature searches using PubMed and reference lists (from inception to 7 ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.577739
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abstract:INTRODUCTION:Cytochromes P450 (P450) and associated monooxygenases are a family of heme proteins involved in metabolism of endogenous compounds (arachidonic acid, eicosanoids and prostaglandins) as also xenobiotics including drugs and environmental chemicals. Liver is the major organ involved in P450-mediated metabolis...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.759208
更新日期:2013-05-01 00:00:00
abstract::Introduction: Chemokine receptors are important therapeutic targets for the treatment of many human diseases. This study will provide an overview of approved chemokine receptor antagonists and promising candidates in advanced clinical trials.Areas covered: We will describe clinical aspects of chemokine receptor antago...
journal_title:Expert opinion on drug metabolism & toxicology
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doi:10.1080/17425255.2020.1711884
更新日期:2020-01-01 00:00:00
abstract:INTRODUCTION:Enzalutamide is the first approved second-generation androgen receptor (AR) antagonist in the treatment of metastatic castration-resistant prostate cancer (mCRPC) with or without docetaxel-based chemotherapy. Over the past 5 years, a number of attempts were made to determine the efficacy of enzalutamide in...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1440288
更新日期:2018-03-01 00:00:00
abstract::Extensive growth in the field of molecular biology in recent decades has led to the development of new and powerful experimental and computational tools that enable the analysis of complex biological responses to chemical exposure on both a functional and structural genetic level. The ability to profile global respons...
journal_title:Expert opinion on drug metabolism & toxicology
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doi:10.1517/17425255.4.11.1379
更新日期:2008-11-01 00:00:00
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journal_title:Expert opinion on drug metabolism & toxicology
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doi:10.1080/17425255.2016.1214711
更新日期:2016-11-01 00:00:00
abstract:INTRODUCTION:Pemphigus is an autoimmune blistering disease of the skin and mucous membranes characterized by the development of autoantibodies against the desmosomal proteins, desmoglein-1 and -3. Before the advent of corticosteroids, therapy was almost fatal. The introduction of high-dose corticosteroid therapy has re...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.542149
更新日期:2011-02-01 00:00:00
abstract:INTRODUCTION:Capecitabine , an oral prodrug of 5-fluorouracil (5-FU), is adsorbed in its intact form through the intestine and metabolized to 5-FU in tumour cells. In metastatic breast cancer (MBC), capecitabine is an effective and well-tolerated therapeutic option both in monotherapy and in combination with chemothera...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.759939
更新日期:2013-02-01 00:00:00
abstract:INTRODUCTION:Iron overload is an inevitable consequence of transfusion therapy for a variety of underlying anemias. Iron overload, without effective chelation, will lead to significant morbidity and mortality. Deferasirox (Exjade®) is an oral tridentate iron chelator used for reducing iron overload. AREAS COVERED:In a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.640674
更新日期:2012-01-01 00:00:00
abstract::Toxicogenomics is the application of gene expression profiling technology to toxicology. This results in the generation of very large and complex gene expression data sets associated with the development of toxicities. It is widely assumed that this data can be deconvoluted to reveal novel insights into toxicological ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.1.2.247
更新日期:2005-08-01 00:00:00
abstract:INTRODUCTION:Emtricitabine/tenofovir disoproxil fumarate fixed-dose combination (FTC/TDF FDC) is the co-formulation of a nucleoside and a nucleotide, respectively. After oral administration, both drugs exhibit plasma and intracellular half-lives suitable for once-daily dosing. Within the host cells, active metabolites ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.714367
更新日期:2012-10-01 00:00:00
abstract:INTRODUCTION:Nucleosidic analogs such as pyrimidine and purine derivatives are mainstay in the field of treating cancers, both in adults and in children. All these drugs act as antimetabolite compounds, that is, they interfere with the ability of cancer cells to synthesize the nucleosides or the nucleotides necessary f...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.985648
更新日期:2015-05-01 00:00:00
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journal_title:Expert opinion on drug metabolism & toxicology
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doi:10.1517/17425255.4.3.237
更新日期:2008-03-01 00:00:00
abstract:INTRODUCTION:The review aims to discuss effects of vitrectomy on pharmacokinetics of anti-vascular endothelial growth factor (anti-VEGF) agents, and attempt to provide treatment guidance. Areas covered: An Embase search was conducted using the terms 'anti-VEGF', 'pegaptanib', 'ranibizumab', 'bevacizumab', 'aflibercept'...
journal_title:Expert opinion on drug metabolism & toxicology
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更新日期:2017-12-01 00:00:00
abstract:INTRODUCTION:In preliminary clinical studies, aleglitazar, a new dual PPAR-α-γ agonist, has been demonstrated to improve hyperglycemia and dyslipidemia in patients with type 2 diabetes mellitus. This review will provide up-to-date information on the clinical safety and efficacy of aleglitazar, which is currently under ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.579561
更新日期:2011-06-01 00:00:00
abstract::Acute kidney injury is a common condition and is associated with a high mortality rate. It has been recognised that routinely used measures of renal function, such as levels of blood urea nitrogen and serum creatinine, increase significantly only after substantial kidney injury occurs and then with a time delay. Insen...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
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更新日期:2006-10-01 00:00:00
abstract:INTRODUCTION:Raltegravir was the first available integrase inhibitor for treating HIV-positive patients. This review aims to provide an overview of its role in the management of HIV-1 infection, highlighting its key pharmacokinetic and pharmacodynamic properties. AREAS COVERED:This review covers material searched and ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1056732
更新日期:2015-07-01 00:00:00
abstract:OBJECTIVE:The objectives of this study are to characterize capsaicin glucuronidation using liver microsomes and to determine the contribution of individual UDP-glucuronosyltransferase (UGT) enzymes to hepatic glucuronidation of capsaicin. METHODS:The rates of glucuronidation were determined by incubating capsaicin wit...
journal_title:Expert opinion on drug metabolism & toxicology
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doi:10.1517/17425255.2014.954548
更新日期:2014-10-01 00:00:00
abstract:INTRODUCTION:The availability of non-vitamin K antagonist oral anti-coagulants alongside vitamin K antagonists has offered a variety of options for anti-coagulation, but has also necessitated a good understanding of the pharmacological properties of each of these drugs prior to their use, to maximise the therapeutic be...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2019.1604686
更新日期:2019-05-01 00:00:00
abstract::The expression of drug-metabolising enzymes is affected by many endogenous and exogenous factors, including sex, age, diet and exposure to xenobiotics and drugs. To understand fully how the organism metabolises a drug, these alterations in gene expression must be taken into account. The central process, the definition...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.3.367
更新日期:2006-06-01 00:00:00
abstract::Background: The liver plays a central role in human drug metabolism. To model drug metabolism, the major cell type of the liver, the hepatocyte, is commonly used. Hepatocytes can be derived from human and animal sources, including pluripotent stem cells. Cell-based models have shown promise in modeling human drug expo...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2019.1558208
更新日期:2019-01-01 00:00:00
abstract:INTRODUCTION:A more concentrated insulin glargine formulation, containing 300 U/mL (Gla-300) was approved in 2015 in the US and Europe for the treatment of diabetes mellitus in adults. AREAS COVERED:This drug evaluation focuses on the pharmacokinetics (PK) and pharmacodynamics (PD) of Gla-300 from studies published up...
journal_title:Expert opinion on drug metabolism & toxicology
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更新日期:2016-08-01 00:00:00