Abstract:
INTRODUCTION:Mortality from invasive fungal disease involving the central nervous system (CNS) is excessive. Achieving therapeutic drug concentrations at the site of infection within the CNS is always difficult and its evaluation is complex due to anatomical barriers and variable pathophysiological lesions. Areas covered: This review provides an updated summary of the CNS PK of antifungal therapies. It considers factors that influence the success of antifungal regimens for CNS infection as well as preclinical and clinical data that quantify antifungal pharmacokinetics (PK) in the CNS. Furthermore, it presents state-of-the-art technologies to enhance the clinical use of existing antifungal drugs, and introduces novel antifungal drugs in development. Expert opinion: The antifungal drugs currently available are either suboptimal, or are being used suboptimally, for CNS disease. Therapeutic drug monitoring is mandatory to enhance their effectiveness. Novel drugs in development may offer more efficacious options. In all cases, contemporary technologies to assess CNS PK offer the opportunity to enhance our understanding and use of antifungal drugs for CNS fungal disease.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Stott KE,Hope Wdoi
10.1080/17425255.2018.1492551subject
Has Abstractpub_date
2018-08-01 00:00:00pages
803-815issue
8eissn
1742-5255issn
1744-7607journal_volume
14pub_type
杂志文章,评审abstract::There is an increasing recognition within the pharmaceutical industry of the importance of the ADME studies in drug registration. Consequently, there has been a drive in recent times to conduct the ADME studies as early as possible in the development programme. There are, however, regulatory barriers, particularly in ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.1.1.23
更新日期:2005-06-01 00:00:00
abstract::Severe adverse drug reactions (ADRs) are a major problem in drug development and clinical practice and the most common cause of market withdrawals of drugs. Individualised drug safety aims at the prospective identification of single patients who carry genetic predispositions for the development of serious or fatal ADR...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.1.3.537
更新日期:2005-10-01 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:Short- and long-acting β agonists (SABA and LABA) are bronchodilators for treating asthma. Bronchodilator response (BDR) is quantified by measuring air expired in the first second during a forced expiratory maneuver, prior to and following inhalation of SABA. BDR has been associated with a significant degr...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.939956
更新日期:2014-09-01 00:00:00
abstract::Irritable bowel syndrome (IBS) is a chronic disease characterized by complex interactions between genetic predisposition and the environment. Current treatments for IBS are characterized by a highly variable response. Gene variations may result from insertions or deletions, gene rearrangements, splice variants or copy...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 社论
doi:10.1517/17425255.2015.1048223
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Although naturally occurring peptides have been widely used as drugs, their rapid in vivo degradation by proteolysis and their interactions at multiple receptors are part of the reason for the limitation of their clinical applications. AREAS COVERED:This paper reviews peptide-metabolizing enzymes in the b...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.574126
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND:Aerosol administration of therapeutics to the respiratory system represents a significant opportunity for many classes of drugs, both small molecules and macromolecules, including recently engineered peptide and protein therapeutics. However, minimally invasive assessment of drug absorption mechanisms in viv...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.4.333
更新日期:2008-04-01 00:00:00
abstract:BACKGROUND:Cytochrome P450 2E1 (CYP2E1) plays a central role in the metabolism and metabolic activation of a large number of small, mostly xenobiotic compounds. These qualities distinguish CYP2E1 from traditional enzymes and pose significant challenges to understanding the role and consequences of CYP2E1-mediated metab...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.8.1053
更新日期:2008-08-01 00:00:00
abstract:INTRODUCTION:The goal of pharmacologic therapy with antiepileptic drugs (AEDs) is to reduce the frequency of seizures and achieve a seizure-free state with minimal side effects. However 30% of patients treated with available AEDs continue to experience uncontrolled seizures. There is still need for new AEDs with enhanc...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1360278
更新日期:2017-09-01 00:00:00
abstract:INTRODUCTION:Many different drugs and xenobiotics (chemical compounds foreign to an organism) can injure the bile duct epithelium and cause inflammatory bile duct diseases (cholangiopathies) ranging from transient cholestasis to vanishing bile duct syndrome, sclerosing cholangitis with development of biliary fibrosis a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.674511
更新日期:2012-05-01 00:00:00
abstract::Introduction: The inclusion of pharmacogenetics alongside clinical information in anticoagulant therapy offers the opportunity for a tailored approach to treatment according to individual patient characteristics. Areas covered: Literature was searched using PubMed database, focusing on pharmacogenetics of oral anticoa...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2019.1623878
更新日期:2019-06-01 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:BACKGROUND:The aim of the study was to evaluate the bioequivalence of two itraconazole 100 mg capsule formulations. RESEARCH DESIGN AND METHODS:The single-center, open-label, randomized, three-period, three-sequence, reference-replicated, cross-over study included 38 healthy subjects under fed conditions. In each stud...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,随机对照试验
doi:10.1080/17425255.2018.1503649
更新日期:2018-09-01 00:00:00
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: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::Pathologists play a central role in the recognition and prevention of drug-induced toxicity. Pathologists engaged in clinical practice must identify a pattern of histological lesions that are interpreted in concert with a variety of clinical data to determine the probability of drug-induced toxicity versus background ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.2.241
更新日期:2006-04-01 00:00:00
abstract:INTRODUCTION:Pharmacogenomics is the field that studies an individualized treatment approach for patients' medication regimen that can impact drug safety, productivity, and personalized health care. Pharmacogenomics characterizes the genetic differences in metabolic pathways which can affect a patient's individual resp...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2016.1209482
更新日期:2016-11-01 00:00:00
abstract:INTRODUCTION:Obesity is an epidemic associated with significant morbidity. Lorcaserin , a novel serotonin 2C receptor antagonist, was recently approved as an adjunct to lifestyle modification for long-term weight loss and maintenance. Clinical studies in patients without diabetes demonstrated 5.8% mean weight loss from...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.798643
更新日期:2013-08-01 00:00:00
abstract:INTRODUCTION:Recent advances in molecular biology have enabled personalized cancer therapies with molecularly targeted agents (MTAs), which offer a promising future for cancer therapy. Dynamic modeling and simulation (M&S) is a powerful mathematical approach linking drug exposures to pharmacological responses, providin...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2016.1141895
更新日期:2016-01-01 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
abstract:INTRODUCTION:There have been increasing concerns regarding adverse reactions and toxicity incidents caused by traditional Chinese medicines (TCMs), among which the nephrotoxicity is particularly worrying. AREAS COVERED:This review summarizes the ingredients with renal toxicity from some TCMs through searching the rele...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2016.1132306
更新日期:2016-01-01 00:00:00
abstract:INTRODUCTION:Co-medication, gene polymorphisms and co-morbidity are main causes for high variability in expression and function of the CYP3A isoenzymes. Pharmacokinetic variability is a major source of interindividual variability of drug effect and response of CYP3A substrates. While CYP3A genotyping is of limited use,...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2016.1163337
更新日期:2016-05-01 00:00:00
abstract:INTRODUCTION:Bioaccessibility is a growing area of research in the field of risk assessment. As polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants, they are the toxicants of focus to establish cancer risks in humans. Orally ingested PAHs also cause toxicity and even affect the pharmacokinet...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.823157
更新日期:2013-11-01 00:00:00
abstract:INTRODUCTION:Integration of targeted therapy and additional chemotherapy options has improved median overall survival (OS) in patients with unresectable metastatic colorectal cancer (mCRC). Cetuximab and panitumumab are examples of targeted therapies, specifically against the epidermal growth factor receptor (EGFR). Th...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1112787
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Epigenetics is a rapidly growing field describing heritable alterations in gene expression that do not involve DNA sequence variations. Advances in epigenetics and epigenomics have influenced pharmacology, leading to the development of a new specialty, pharmacoepigenetics, the study of the epigenetic basis...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1260546
更新日期:2017-04-01 00:00:00
abstract:INTRODUCTION:Small molecule tyrosine and serine-threonine kinase inhibitors (TKIs and STKIs) are emerging drugs that interfere with downstream signaling pathways involved in cancer proliferation, invasion, metastasis and angiogenesis. The understanding of their pharmacokinetics, the identification of their transporters...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1006626
更新日期:2015-05-01 00:00:00
abstract::The interaction between drug-metabolising enzymes and active transporters is an emerging concept in pharmacokinetics. In the gut mucosa, P-glycoprotein and cytochrome P450 (CYP)3A functionally interact in three ways: i) drugs are repeatedly taken up and pumped out of the enterocytes by P-glycoprotein, thus increasing ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.1.4.641
更新日期:2005-12-01 00:00:00
abstract::Valproate (2-propylpentanoate) is available as valproic acid, sodium valproate and semisodium valproate. It has actions on dopamine, GABA and glutamate neurotransmission and intracellular signaling. Its main psychiatric use is to treat bipolar disorder. It has been used in other psychiatric disorders, including schizo...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250902911455
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:The importance of transporters in drug disposition and response has led to increasing interest in genetic variations and expression differences of their genes. OBJECTIVE:This review summarizes: i) genetic variations in transporters and associated drug response; and ii) a pharmacogenomic approach to correlat...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.3.237
更新日期:2008-03-01 00:00:00
abstract::Introduction: Overactive bladder (OAB) has a heterogeneous presentation that varies between individuals and by gender. Treatment with antimuscarinic medications is standard first line pharmacotherapy for most patients with OAB. However, gender specific differences in the pharmacokinetics and pharmacodynamics of antimu...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2020.1714591
更新日期:2020-02-01 00:00:00