Abstract:
BACKGROUND:Hepatocellular carcinoma (HCC) is among the world's most common cancers. For over ten years, the only medical treatment for it has been the multikinase inhibitor Sorafenib. Currently, however, other first or second-line therapeutic options have also shown efficacy against HCC, such as multikinase inhibitors (Regorafenib, Lenvatinib, and Cabozantinib), a monoclonal antibody against the vascular endothelial growth factor receptor 2 (Ramucirumab), and immune-checkpoint inhibitors (Nivolumab, Pembrolizumab, Ipilimumab). AIM:The aim of this paper is to review the metabolic pathways of drugs that have been tested for the treatment of HCC and the potential influence of liver failure over those pathways. METHODS:The Food and Drug Administration (FDA)'s and European Medicines Agency (EMA)'s datasheets, results from clinical trials and observational studies have been reviewed. RESULTS:This review summarizes the current knowledge regarding targets, metabolic pathways, drug interactions, and adverse events of medical treatments for HCC in cirrhotic patients. CONCLUSION:The new scenario of systemic HCC therapy includes more active drugs with different metabolic pathways and different liver adverse events. Clinical and pharmacological studies providing more data on the safety of these molecules are urgently needed.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Galati G,Massimo Vainieri AF,Maria Fulgenzi CA,Di Donato S,Silletta M,Gallo P,Onorato A,Vespasiani-Gentilucci U,Picardi Adoi
10.2174/1389200221999200918141239subject
Has Abstractpub_date
2020-01-01 00:00:00pages
866-884issue
11eissn
1389-2002issn
1875-5453pii
CDM-EPUB-110084journal_volume
21pub_type
杂志文章abstract::Arachidonic acid (AA) is metabolized by enzymes of the cytochrome P450 (CYP) 4A and CYP4F subfamilies to 20- hydroxyeicosatetraeonic acid (20-HETE), which plays an important role in the cardiovascular system. In the current work, we reviewed the formation of 20-HETE in different species by different CYPs; 20-HETE meta...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200211314060007
更新日期:2013-07-01 00:00:00
abstract::Several epidemiological studies throughout the years have suggested that polyphenols from fruits and vegetables promote health and reduce the risk of certain chronic and neurodegenerative diseases. Yet, it has been proved to be extremely difficult to quantitatively establish the benefit afforded by polyphenols, princi...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200214666131210144115
更新日期:2014-01-01 00:00:00
abstract::Infection with the human immunodeficiency virus type 1 (HIV) results in a chronic infection that progressively cripples the host immune defenses. HIV infection is associated with increased tryptophan (trp) catabolism by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO). IDO has powerful immune suppressiv...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920007780362527
更新日期:2007-04-01 00:00:00
abstract:BACKGROUND:Glioblastoma multiforme, one of the most aggressive brain tumors, has a very poor clinical outcome. Despite the introduction of the alkylating reagent temozolomide (TMZ) to surgery and radiotherapy, the survival of patients could only be modestly increased up to less than 15 months. Therefore, innovative tre...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200217666160607232540
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:In the last few years, the use of modified Carbon Nanomaterials (CNMs) for theranostics (therapeutic and diagnosis) applications is a new and rapidly growing area in pharmacy and medical fields. Owing to this, their specific physicochemical behaviors like high stability, drug loading, surface area to volume ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666180925094515
更新日期:2019-01-01 00:00:00
abstract::The in vivo hepatic clearance of tanshinone IIA in the rat was predicted using microsome, cytosol and S9 fractions combined with two different cofactor systems, NADPH-regenerating and UDPGA system. Two different models, the well stirred model and the parallel-tube model, were used in predicting the in vivo clearance i...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920008783331103
更新日期:2008-01-01 00:00:00
abstract::Modern biologics are biotechnology-derived pharmaceuticals. They are mostly used for diagnosis, prevention and treatment of serious and chronic diseases. Today, therapeutic biologics range from traditional biologics like blood and blood components, fractionated blood products, and antitoxins to modern biologics such a...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920006774832604
更新日期:2006-01-01 00:00:00
abstract::To understand the sophisticated dynamic behaviors of drug elution and permeation in the gastrointestinal tract (GIT), researchers have tried to reemerge it by employing various in vitro experimental models. However, official in vitro apparatuses routinely used for quality control purposes, employ simple, non-physiolog...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200216666150812123836
更新日期:2015-01-01 00:00:00
abstract::Cytochrome P450s (P450 or CYPs) comprise a superfamily of enzymes that catalyze the oxidation of a wide variety of xenobiotic chemicals. Although most of P450 inhibitors decrease the metabolic activities mediated by the corresponding P450 forms, unexpected phenomena, which are called as activation or heterotropic coop...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008784746364
更新日期:2008-06-01 00:00:00
abstract::Graphene and its modified nano-composites have gained much attention in recent times in cancer therapy as nanotheranostics due to low production cost, ease in synthesis and physicochemical properties (ultra-large surface area with planar structure and π-π conjugation with the unsaturated and aromatic drugs/biomolecule...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200215666141125120633
更新日期:2015-01-01 00:00:00
abstract::Photodynamic therapy (PDT) combines photosensitizer, visible light and oxygen, which has the characteristics of high selectivity, minimal invasiveness, low side effect, and allowing repetitive application. The photophysics and mechanisms leading to cell death mediated by PDT have been studied extensively, and PDT has ...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920009790274559
更新日期:2009-10-01 00:00:00
abstract::This review focuses primarily on the mammalian medium and long-chain fatty acid coenzyme A ligases that have been implicated in the metabolism of xenobiotic carboxylic acids such as pesticides, arylpropionate non steroidal anti-inflammatory drugs and the hypolipidaemic clofibrate and its congeners. Evidence of multipl...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200003339261
更新日期:2000-07-01 00:00:00
abstract::It has long been suggested that some of the neuropharmacological, neurochemical and behavioural effects of ethanol are mediated by its first metabolite, acetaldehyde. In spite of the well documented psychoactivity of acetaldehyde, the precise role of this compound in alcohol abuse remains a matter of intense debate am...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920007782109797
更新日期:2007-10-01 00:00:00
abstract::Recently, it was found that mutations in the binding cavity of drug-metabolizing Cytochrome P450 BM3 mutants can result in major changes in regioselectivity in testosterone (TES) hydroxylation. In the current work, we report the intrinsic reactivity of TES' C-H bonds and our attempts to rationalize experimentally obse...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920012798918471
更新日期:2012-02-01 00:00:00
abstract::Brain, the centre of the nervous system and an integral part the body, is protected by two anatomical and physiological barriers- Blood-Brain Barrier (BBB) and Blood-Cerebrospinal Fluid Barrier (BCSFB). Blood-Brain Barrier is a very complex and highly organized multicellular structure that shields the brain from harmf...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200218666170113125132
更新日期:2017-01-01 00:00:00
abstract::The nature and level of systemic exposure to the active herbal constituents will profoundly affect their effects at action sites, which is fundamental in understanding their roles in the overall beneficial effects of a herbal medicine. The objective of this study is to gain a full picture of the systemic exposure to v...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200211209050494
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Medical application of nanotechnology is termed as Nanomedicine and is widely used in healthcare industries. Nanotechnology has helped Physicians, Scientists and Technologists to understand the changes in cellular levels to develop nanomedicines and address the challenges faced by the healthcare sectors. Nan...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666180305154119
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVE:Tyrosine kinase inhibitors (TKIs) are widely used drugs which have high availability in reducing the activity of BCR-ABL1 tyrosine kinase, therefore they play an indispensable role in the treatment of Chronic myeloid leukemia (CML). Imatinib, dasatinib and nilotinib have been proved to have absolute bioavaila...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200218666170116113705
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:In recent times, herbals or phytomedicines have become very popular due to their global acceptance as a complementary and alternative remedy. While modern drugs are commercially available only after laboratory validations, clinical trials, as well as approval from drug regulatory authorities, majority of the...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200220666190325141422
更新日期:2019-01-01 00:00:00
abstract::Glucuronidation represents a major pathway which enhances the elimination of many lipophilic xenobiotics and endobiotics to more water-soluble compounds. The UDP-glucuronosyltransferase (UGT) family catalyzes the glucuronidation of the glycosyl group of a nucleotide sugar to an acceptor compound (aglycone) at a nucleo...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200003339171
更新日期:2000-09-01 00:00:00
abstract::Bioavailability of orally administered drugs can be influenced by a number of factors including release from the formulation, dissolution, stability in the gastrointestinal (GI) environment, permeability through the gut wall and first-pass gut wall and hepatic metabolism. Although there are various enzymes in the gut ...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920010794328913
更新日期:2010-11-01 00:00:00
abstract:BACKGROUND:The red-crowned crane (Grus japonensis) is one of the most vulnerable bird species in the world. Mycotoxins are toxic secondary metabolites produced by fungi and considered naturally unavoidable contaminants in animal feed. Our recent survey indicated that the mycotoxins had the potential to contaminate redc...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666200726221126
更新日期:2020-01-01 00:00:00
abstract::P-glycoprotein (P-gp) is involved in MDR and in neurodegenerative disorders such as Parkinson disease (PD), Alzheimer disease (AD) and epilepsy. Cytochrome P450 enzymes (CYP450s) catalyze the metabolism of a wide variety of endogenous and exogenous compounds including xenobiotics, drugs, environmental toxins, steroids...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920011798357015
更新日期:2011-10-01 00:00:00
abstract::A amyloid-β (Aβ) plaque formation in the brain is known to be the root cause of Alzheimer's disease (AD), which affects the behavior, memory, and cognitive ability in humans. The brain starts undergoing changes several years before the actual appearance of the symptoms. Nanotechnology could prove to be an alternative ...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666201124140518
更新日期:2020-01-01 00:00:00
abstract::New chemical entities are routinely screened in vitro and in vivo for their ability to induce cytochrome P450s (CYP), other drug-metabolizing enzymes and possibly transporters in an attempt to more accurately predict clinical parameters such as drug-drug interactions and clearance in humans. Some of these potential th...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200033489352
更新日期:2003-10-01 00:00:00
abstract:: ...
journal_title:Current drug metabolism
pub_type: 社论
doi:10.2174/138920021914181211113837
更新日期:2018-01-01 00:00:00
abstract::We report here a comprehensive evaluation of the effects of culture duration on the gene expression of P450 isoforms, uptake transporters and efflux transporters in human hepatocyte cultured in the absence and presence of the prototypical proinflammatory cytokine, interleukin-6 (IL-6). Primary collagen-matrigel sandwi...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920012802138570
更新日期:2012-09-01 00:00:00
abstract::When used at a high dose, many anticancer drugs produce undesirable side effects including hepatotoxicity. Transdermal delivery bypasses first-pass metabolism, allowing the use of a lower dose of drug while decreasing systemic toxicity. In this review, we summarize various advanced technologies for improving anticance...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008785821693
更新日期:2008-09-01 00:00:00
abstract:BACKGROUND:Painful peripheral neuropathy is a dose-limiting adverse effect of the antitumor drug oxaliplatin. The main symptoms of neuropathy: tactile allodynia and cold hyperalgesia, appear in more than 80% of patients on oxaliplatin therapy and are due to the overexpression of neuronal sodium channels (Navs) and neur...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666200711155632
更新日期:2020-01-01 00:00:00
abstract::Knowledge regarding cytochrome P450 (P450) is crucial to the fields of drug therapy and drug development, as well as in our understanding of the mechanisms underlying the metabolic activation of potentially toxic and carcinogenic compounds. Escherichia coli is the most extensively utilized host in the production of re...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920006776873472
更新日期:2006-05-01 00:00:00