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 metabolism and hepatic enzymes have been characterized. Extrahepatic organs, such as lung, kidney and brain have the capability for biotransformation through P450 enzymes. Brain, including human brain, expresses P450 enzymes that metabolize xenobiotics and endogenous compounds. AREAS COVERED:An overview of P450-mediated metabolism in brain is presented focusing on distinct differences seen in expression of P450 enzymes, generation of unique P450 enzymes in brain through alternate splicing and their consequences in terms of metabolism of psychoactive drugs and inflammatory prompts, such as leukotrienes, thus modulating inflammatory response. EXPERT OPINION:The brain possesses unique P450s that metabolize drugs and endogenous compounds through pathways that are markedly different from that seen in liver indicating that extrapolation directly from liver to brain is not appropriate. It is therefore necessary to characterize the unique brain P450s and their ability to metabolize xenobiotics and endogenous compounds to better understand the functions of this important class of enzymes in brain, especially human brain.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Ravindranath V,Strobel HWdoi
10.1517/17425255.2013.759208subject
Has Abstractpub_date
2013-05-01 00:00:00pages
551-8issue
5eissn
1742-5255issn
1744-7607journal_volume
9pub_type
杂志文章,评审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: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:Golimumab is a human anti-TNF monoclonal antibody that was derived from human antibody-transgenic mice. Golimumab demonstrated meaningful clinical benefit and tolerable safety in patients with active rheumatoid arthritis (RA) who were methotrexate (MTX)-naïve, or who inadequately responded to MTX or who ha...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2016.1146682
更新日期:2016-01-01 00:00:00
abstract:INTRODUCTION:Neonatal patients, because of the inability of their immune system to properly respond to microbial challenge, are highly susceptible to viral infections. Immunoglobulins, monoclonal antibody and antiviral drugs are used for prophylaxis and treatment of viral diseases in neonates. Neonates and, especially,...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1108963
更新日期:2015-01-01 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
pub_type: 杂志文章,评审
doi:10.1080/17425255.2016.1202916
更新日期:2016-08-01 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:INTRODUCTION:Organic anion transporting polypeptide (OATP) uptake transporters are important for the disposition of many drugs and perturbed OATP activity can contribute to adverse drug reactions (ADRs). It is well documented that both genetic and environmental factors can alter OATP expression and activity. Genetic fa...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.656087
更新日期:2012-03-01 00:00:00
abstract:INTRODUCTION:Various trials have attempted to develop gene expression profiles (GEPs) that may provide a better predictor of clinical outcome over traditional clinicopathological criteria. AREAS COVERED:The review focuses on two main areas: trials examining chemotherapy-induced GEP changes pre- and post-treatment, and...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.694867
更新日期:2012-09-01 00:00:00
abstract:INTRODUCTION:Assessments of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics are an integral part in the development of novel therapeutic agents. Compared with traditional small molecule drugs, therapeutic proteins possess many distinct PK/PD features that necessitate the application of modified or separate ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1041917
更新日期:2015-07-01 00:00:00
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: The treatment of psoriasis with conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) is often linked to unsatisfactory outcomes and the risk of serious adverse events. Over the last decades, research advances in understanding the role of tumor necrosis factor alpha (TNF α) a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2019.1681969
更新日期:2019-11-01 00:00:00
abstract:INTRODUCTION:Cervical cancer is the second-most common malignancy in women worldwide. Cisplatin was introduced as a radiosensitizer in 1999 to improve chances of survival. Tumor cell hypoxia, however, remains a major limiting factor in the treatment of solid tumors with chemotherapy and radiation. There has since been ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.730518
更新日期:2012-12-01 00:00:00
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-...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.832755
更新日期:2013-11-01 00:00:00
abstract:INTRODUCTION:In vitro genotoxicity assays have a high sensitivity to detect rodent carcinogens, but mammalian cell tests have a propensity for misleading positive results (poor specificity). Recent data show a greater risk of misleading positive results in p53-deficient rodent cell lines than in p53-competent human cel...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.627855
更新日期:2011-12-01 00:00:00
abstract:INTRODUCTION: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 presen...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2019.1588885
更新日期:2019-04-01 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
更新日期:2011-08-01 00:00:00
abstract:INTRODUCTION:Drug ototoxicity represents one of the main preventable causes of deafness. Ototoxicity is a trait shared by aminoglycoside and macrolide antibiotics, antimalarial medications, loop diuretics, platinum-based chemotherapeutic agents, some NSAIDs and most recently described, acetaminophen when abused with na...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.614231
更新日期:2011-12-01 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:BACKGROUND:The number of patients eligible for cardiovascular therapies in general is forecast to increase substantially in the coming decades. However, the current list of potential future cardiovascular blockbuster drugs is alarmingly short. There is thus a clear need for innovative strategies to increase the efficie...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.6.665
更新日期:2008-06-01 00:00:00
abstract:INTRODUCTION:Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of T-cell neoplasms. Most patients with PTCL have a poor outcome with conventional therapies and are not cured without stem-cell transplantation. Pralatrexate, a novel antifolate chemotherapeutic agent, was rationally designed to impede folate m...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.595404
更新日期:2011-09-01 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: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::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:This meeting report presents a brief summary on the 4th Annual Predictive Toxicology Summit 2012, which was held on 15 - 16 February 2012 in London. AREAS COVERED:The majority of presentations came from global pharmaceutical companies, although small and medium enterprise (SME) and academic researchers we...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1517/17425255.2013.802306
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND:A growing body of evidence suggests that everolimus might offer effective immunosuppressive activity together with antiproliferative effects that may address some of the unmet needs in the long-term therapeutic management of the post-transplant patient. OBJECTIVE:To summarize the emerging evidence for emplo...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.6.807
更新日期:2008-06-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Iloperidone is a newly commercialized second-generation (atypical) antipsychotic approved for the acute treatment of schizophrenia in adults. AREAS COVERED IN THIS REVIEW:the purpose of this review is to describe the pharmacokinetic profile of iloperidone and its clinical implications in the tr...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2010.531259
更新日期:2010-12-01 00:00:00
abstract:INTRODUCTION:Despite increasing early detection and treatment of prostate cancer, a subset of patients presents with or develops metastatic disease. Androgen deprivation therapy is effective but resistance eventually develops, resulting in a lethal phenotype known as castration-resistant prostate cancer (CRPC). Recentl...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.789019
更新日期:2013-07-01 00:00:00
abstract::There is wide inter-individual variability in the pharmacokinetics, pharmacodynamics and tolerance of anticancer drugs. Recent evidence suggests that there is even greater variability between individuals of different ethnicity. Allelic variants of genes encoding drug metabolising enzymes are expressed with different i...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250902800153
更新日期:2009-03-01 00:00:00
abstract:INTRODUCTION:The pharmacokinetic properties of anti-infective drugs are a determinant part of treatment success. Pathogen replication is inhibited if adequate drug levels are achieved in target sites, whereas excessive drug concentrations linked to toxicity are to be avoided. Anti-infective distribution can be predicte...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1037278
更新日期:2015-01-01 00:00:00
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 channe...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2010.523420
更新日期:2010-12-01 00:00:00