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 for proliferation and progression. As with most cytotoxics, maintaining patients in their therapeutic window is challenging, and predicting changes in drug exposure is critical to ensure an optimal efficacy/toxicity balance. AREAS COVERED:Among the antimetabolites, a small but widely prescribed number of drugs (i.e., gemcitabine, capecitabine, cytarabine, azacytidine) share a same metabolic pattern driven by a liver enzyme, cytidine deaminase (CDA), coded by a gene displaying several genetic and epigenetic polymorphisms. Consequently, CDA activity is erratic, ranging from deficient to ultra-rapid deaminator patients, with subsequent impact on drug pharmacokinetics and pharmacodynamics eventually. This review provides an update on the variety of clinical studies and case-reports investigating on CDA status as a marker for clinical outcome in cancer patients treated with nucleosidic analogs. EXPERT OPINION:Whereas sorting patients on the basis of their CDA genotype remains tricky because of unclear genotype-to-phenotype relationships, developing functional strategies (i.e., phenotype-based status determination) could help to use CDA status as a biomarker for developing adaptive dosing strategies with nucleosidic analogs.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Serdjebi C,Milano G,Ciccolini Jdoi
10.1517/17425255.2015.985648subject
Has Abstractpub_date
2015-05-01 00:00:00pages
665-72issue
5eissn
1742-5255issn
1744-7607journal_volume
11pub_type
杂志文章,评审abstract:INTRODUCTION:Dosing of antibiotics in people with cystic fibrosis (CF) is challenging, due to altered pharmacokinetics, difficulty of lung tissue penetration, and increasing presence of antimicrobial resistance. AREAS COVERED:The purpose of this work is to critically review original data as well as previous reviews an...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2021.1836157
更新日期:2021-01-01 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
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abstract:INTRODUCTION:Selective serotonin reuptake inhibitors (SSRIs) are commonly used to manage antenatal depression. Hence, the aim of this systematic review is to assess the prevalence of birth defects associated with pregnancy exposure to such agents and summarize the hypothesized teratogenic mechanisms. AREAS COVERED:Med...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
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更新日期:2015-01-01 00:00:00
abstract::The calcium sensing receptor (CaSR) is expressed in cells secreting calcium-regulating hormones, in cells involved in calcium transport and in many other tissues, with an as yet not completely defined role. In parathyroid cells, the CaSR stimulation inhibits parathyroid hormone (PTH) secretion, synthesis and parathyro...
journal_title:Expert opinion on drug metabolism & toxicology
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abstract:INTRODUCTION:Epilepsy is a chronic neurological disease manifesting as recurrent seizures. Despite the availability of numerous antiepileptic drugs (AEDs), one-third of the patients are not responsive to treatment. Such inter-individual variability in the response to AEDs may be partly explained by genetic differences....
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.872630
更新日期:2014-03-01 00:00:00
abstract:INTRODUCTION:Multiple myeloma (MM) patients who relapse, or become refractory to currently available novel agents, have limited treatment options with poor outcomes. The introductions of the newer proteasome inhibitor carfilzomib and the immunomodulatory agent pomalidomide have provided new treatment strategies within ...
journal_title:Expert opinion on drug metabolism & toxicology
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更新日期:2013-11-01 00:00:00
abstract::Antithrombotic therapy is a crucial component of interventional cardiology and currently involves the administration of both anticoagulant and antiplatelet agents. The implementation of standard dual or triple antiplatelet therapies has allowed percutaneous coronary intervention (PCI) with stent implantation to become...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
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更新日期:2007-08-01 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
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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:Drug metabolism is one of the most important processes involving a drug after administration. Undesirable pharmacokinetic properties may lead to drug discontinuation. In the past several decades, a number of drugs have been withdrawn from the market due to safety issues caused by metabolites, especially re...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
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更新日期:2018-10-01 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:OBJECTIVES:A medical need remains for a once-daily insulin with 24-h basal coverage in all patients. We characterize the steady-state (SS) pharmacokinetic/pharmacodynamic properties of insulin degludec (IDeg) versus insulin glargine (IGlar). RESEARCH DESIGN AND METHODS:In this controlled, single-center study, 66 type ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,随机对照试验
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更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Arterial and venous thrombotic states, including myocardial infarction (MI), stroke and deep vein thrombosis with subsequent pulmonary embolism, are a significant cause of cardiovascular mortality and morbidity. Factor Xa (FXa) plays a pivotal role in thrombus formation. Its inhibition following acute coro...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.688026
更新日期:2012-07-01 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:Extensive within-population variability is the essence of neonatal pharmacology. Despite this, infants remain one of the last therapeutic orphans. Together with additional legal initiatives, tailoring of already available tools (modeling, covariates, pharmacovigilance) may significantly improve pharmacothe...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.931937
更新日期:2014-08-01 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:Chronic constipation is a frequent condition often treated pharmacologically. The laxatives available belong to very different pharmacologic groups. AREAS COVERED:This is a short but comprehensive review of the pharmacology, efficacy and safety of currently available laxatives for chronic constipation. Pe...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.773972
更新日期:2013-04-01 00:00:00
abstract::Introduction: In quantitative modeling, the resolving of underpredictions and overpredictions of hepatic clearance (CLh) makes a top priority for pharmacokinetic modelers. Clearly, the 'protein-mediated hepatic uptake' is a violation of 'the free drug hypothesis', but the lack of its consideration in CLh-predictive ap...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2019.1640679
更新日期:2019-08-01 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: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 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: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
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journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
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更新日期:2016-10-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2011-07-01 00:00:00
abstract:INTRODUCTION:Omalizumab is a subcutaneously administrated monoclonal anti-IgE antibody indicated in adults, adolescents and children 6 years of age and older with moderate to severe allergic asthma uncontrolled by conventional pharmacological treatments and sensitization to at least one perennial allergen. Area covered...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2016.1248403
更新日期:2016-12-01 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
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更新日期:2008-07-01 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
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更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:CYP enzymes from the CYP2C and CYP2J subfamilies metabolize arachidonic acid in a regiospecific and stereoselective manner to eight epoxyeicosatrienoic acids (EETs). Various EETs have been detected in the liver, as well as in many extrahepatic tissues, and have been implicated in numerous physiological funct...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
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更新日期:2009-07-01 00:00:00
abstract:INTRODUCTION:Mathematical models of dermal transport offer the advantages of being much faster and less expensive than in vitro or in vivo studies. The number of methods used to create such models has been increasing rapidly, probably due to the steady rise in computational power. Although each of the various approache...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
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更新日期:2015-01-01 00:00:00