Abstract:
INTRODUCTION:Despite initial patient benefit, drug resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs) is inevitable. One of the key mechanisms responsible for the development of acquired drug resistance is the secondary T790M missense mutation in exon 20 of the EGFR kinase domain. Afatinib is an ATP-competitive small molecule inhibitor that potently and irreversibly inhibits EGFR and mutated EGFR including the T790M variant, as well as other members of the ErbB family in preclinical studies. AREAS COVERED:The authors describe the rationale and provide the preclinical background to afatinib and its potential as a NSCLC therapy. Specifically, the authors detail the drug's pharmaco-kinetic profile and review its clinical efficacy and toxicity profile. EXPERT OPINION:Afatinib is an effective treatment option for therapy-naive advanced NSCLC harboring an activating EGFR mutation. Furthermore, it is also of potential benefit to patients with acquired resistance to EGFR kinase inhibitors. In the future, the authors envision the clinical development of third-generation EGFR mutation-specific inhibitors in NSCLC, which may potentially spare normal tissue toxicity. Nevertheless, afatinib currently represents a bona fide treatment option in the NSCLC therapeutic armamentarium.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Yap TA,Popat Sdoi
10.1517/17425255.2013.832755subject
Has Abstractpub_date
2013-11-01 00:00:00pages
1529-39issue
11eissn
1742-5255issn
1744-7607journal_volume
9pub_type
杂志文章,评审abstract:INTRODUCTION:Piperine has various pharmacological effects and can modulate the functional activity of metabolic enzymes and drug transporters. Consequently, there is a great interest in the application of piperine as an alternative medicine or bioavailability enhancer. Areas covered: This review deals with the effects ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1418854
更新日期:2018-01-01 00:00:00
abstract:INTRODUCTION:multiple myeloma (MM) is a plasma cell disorder that represents the second most frequent hematologic cancer. Although MM is still an incurable disease, prognosis has improved in the last decades thanks to the introduction of novel agents such as proteasome inhibitors (PIs), immunomodulatory drugs, monoclon...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1417388
更新日期:2018-01-01 00:00:00
abstract:INTRODUCTION:Treatments for hepatitis C virus (HCV) infection have advanced rapidly in the last decade. Pegylated interferon alpha 2a (PEG-IFN alpha 2a) alone, in combination with ribavirin and with or without direct acting antivirals (DAAs) is modestly effective in the treatment of chronic HCV infection. Areas covered...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1421173
更新日期:2018-02-01 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:INTRODUCTION:Pregabalin is an alternative compound to SSRIs and SNRIs for the first-line treatment of generalized anxiety disorder (GAD). Areas covered: We describe the pharmacokinetic properties of pregabalin and their implications for the treatment of GAD. A search in the main database sources (Medline, ISI, Web of K...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1281247
更新日期:2017-03-01 00:00:00
abstract:INTRODUCTION:Mepolizumab is a humanized monoclonal antibody that binds to and inactivates IL-5. It is available as a subcutaneous preparation. The practical application of mepolizumab is as an add-on therapy in the treatment of severe eosinophilic asthma. Areas covered: This article was created from a comprehensive lit...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1406919
更新日期:2017-12-01 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
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.683859
更新日期:2012-06-01 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:BACKGROUND:The intestinal epithelial membrane expresses ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp), multi-drug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP), in addition to various solute carrier (SLC) transporters. These ABC transporters affect the oral bi...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.7.923
更新日期:2008-07-01 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
更新日期:2006-08-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:The prevalence of acute renal allograft rejection has decreased substantially in past decades due to new and more specific immunosuppressive compounds but improvements in long-term graft function have not been achieved. There is a large need for new immunosuppressive agents that lack toxicity of...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.540238
更新日期:2011-01-01 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: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
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1404987
更新日期:2017-12-01 00:00:00
abstract:INTRODUCTION:The prevalence of obesity and associated co-morbid conditions is increasing globally. Physiological changes accompanying obesity are likely to result in altered drug pharmacokinetics; however, there is paucity of information on how to best dose adjust for the obese. AREAS COVERED:This review presents mate...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.570331
更新日期:2011-06-01 00:00:00
abstract:INTRODUCTION:Donepezil is a highly selective acetylcholinesterase inhibitor and one of the only four drugs currently approved for treatment of Alzheimer's dementia. Providing high bioavailability and a very long half-time, donepezil is regarded as effective and well tolerable in Alzheimer's disease patients, even in di...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.915028
更新日期:2014-07-01 00:00:00
abstract:INTRODUCTION:Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy. However, ∼ 30% of patients do not remain seizure free. It is possible that methylxanthine derivatives (e.g., caffeine and theophylline) may partially account for this outcome. AREAS COVERED:Data on the convulsive activity of methylx...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.920822
更新日期:2014-07-01 00:00:00
abstract:BACKGROUND:Anticancer drugs are characterized by a narrow therapeutic window and significant inter-patient variability in therapeutic and toxic effects. Current body surface area (BSA)-based dosing fails to standardize systemic anticancer drug exposure and other alternative dosing strategies also have their limitations...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.10.1307
更新日期:2008-10-01 00:00:00
abstract:INTRODUCTION:Catechins of green tea extract (GTE) have been associated with the rare risk of hepatotoxicity in a few individuals. As GTE were coadministered with synthetic drugs in some hepatotoxicity cases, uncertainty emerged whether GTE are a risk factor of drug-induced liver injury (DILI). AREAS COVERED:Case repor...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.971011
更新日期:2014-12-01 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:INTRODUCTION:Boceprevir is an NS3/NS4A serine protease inhibitor that was approved for use in Hepatitis C virus (HCV) genotype 1 patients by the US Food and Drug Administration (FDA) in May 2011. The approval of this protease inhibitor marked a major paradigm shift in the treatment of HCV, as it was one of the first of...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.840290
更新日期:2013-12-01 00:00:00
abstract:INTRODUCTION:The association between pregnancy and altered drug pharmacokinetic (PK) properties is acknowledged, as is its impact on drug plasma concentrations and thus therapeutic efficacy. However, there have been few robust PK studies of antimalarial use in pregnancy. Given that inadequate dosing for prevention or t...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2020.1802425
更新日期:2020-09-01 00:00:00
abstract:INTRODUCTION:Idiosyncratic drug-induced agranulocytosis (IDIAG) is a life-threatening adverse reaction characterized by an absolute neutrophil count < 500 cells/μl of blood. It shares many of the characteristics of other idiosyncratic drug reactions (IDRs), and this presumably reflects mechanistic similarities. AREAS ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.985649
更新日期:2015-02-01 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:Therapeutic hypothermia is being employed clinically due to its neuro-protective benefits. Both critical illness and therapeutic hypothermia significantly affect drug disposition, potentially contributing to drug-therapy and drug-disease interactions. Currently, there is limited information on the known al...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.574127
更新日期:2011-07-01 00:00:00
abstract::The burden of seasonal influenza in children is poorly recognized, in spite of the potential for severe and even life-threatening illness and common secondary complications. Children are a primary reservoir for the spread of influenza to both family members and the community, which imposes a sizeable social and econom...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.3.5.755
更新日期:2007-10-01 00:00:00
abstract:INTRODUCTION:The second-line treatment of endometriosis-related pain symptoms includes injectable depot formulations of gonadotropin-releasing hormone analogs (GnRH-as). These drugs improve the symptomatology by inducing a hypoestrogenic status and a consequent regression of endometriotic implants. However, GnRH-a may ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2020.1789591
更新日期:2020-09-01 00:00:00
abstract:INTRODUCTION:Gut microbiota plays critical roles in drug metabolism. The variation of gut microbiota contributes to the interindividual differences toward drug therapy including drug-induced toxicity and efficacy. Accordingly, the investigation and elucidation of gut microbial impacts on drug metabolism and toxicity wi...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2016.1121234
更新日期:2016-01-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:The use of the first generation non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) as a component of first-line antiretroviral therapy has been accepted worldwide. EFV is the only antiretroviral agent currently on the market that has been combined with emtricitabine and tenofovir dis...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903483207
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Chemoprevention of cancer refers to the use of natural or synthetic compounds to abolish or perturb a variety of steps in tumor initiation, promotion, and progression. This can be realized through different mechanisms, including activation of free radical scavenging enzymes, control of chronic inflammation...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2021.1839412
更新日期:2021-01-01 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
pub_type: 杂志文章
doi:10.1517/17425255.2014.954548
更新日期:2014-10-01 00:00:00