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, and fatty acids. P-gp substrates, inhibitors and inducers should be designed and developed studying interacting mechanism with both P-gp an CYP450 enzymes before they could be employed in MDR and/or in neurodegenerative disorders. Here, the ex vivo rat everted gut sac assay has been proposed as an immediate approach to simultaneously study metabolism and transport of drugs. Elacridar, verapamil and cyclosporine A (CsA), P-gp inhibitor, substrate and modulator respectively, have been tested to validate this ex vivo approach. The new model have been used yet to develop our ligands MC18, MC266 and MC80, both as potential drugs for MDR and radiotracers for diagnosis of neurodegenerative disorders. Herein, a comparative evaluation of transport and metabolic results, by using in vitro, ex vivo and in vivo assays, is reported.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Inglese C,Perrone MG,Berardi F,Perrone R,Colabufo NAdoi
10.2174/138920011798357015subject
Has Abstractpub_date
2011-10-01 00:00:00pages
702-12issue
8eissn
1389-2002issn
1875-5453pii
BSP/CDM/E-Pub/000146journal_volume
12pub_type
杂志文章abstract::Metabolism of xenobiotics is often seen as an exclusive function of the liver, but some current findings support the notion that the lungs, kidneys and intestine may contribute considerably. After the establishment of the use of liver slices as a useful in vitro model to study metabolism and toxicity of xenobiotics, t...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200023338071
更新日期:2002-02-01 00:00:00
abstract::Molecules exist as three dimensional structures. Therefore they can exist in symmetrical and asymmetrical forms. Molecules with an asymmetric centre are chiral. If the molecule and its mirror image are non-superimposable, the relationship between the two molecules is enantiomeric and the two stereoisomers are enantiom...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200013338810
更新日期:2001-03-01 00:00:00
abstract::During the lifetime, our cells encounter many challenges to their own existence. The survival of organisms and cells depends on the interplay within a complex, yet precisely orchestrated network of proteins. Since the discovery of the Rel/NF-kappaB family of transcription factors, the research has never come to a stop...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920010791196283
更新日期:2010-03-01 00:00:00
abstract::Arylamine N-acetyltransferases (NAT) are xenobiotic-metabolizing enzymes responsible for the acetylation of many aromatic arylamine and heterocyclic amines, thereby playing an important role in both detoxification and activation of numerous drugs and carcinogens. Two closely related isoforms (NAT1 and NAT2) have been ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008784892092
更新日期:2008-07-01 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::Despite the introduction of newer drugs, the atypical antipsychotic clozapine remains the most effective drug in psychotic patients who are resistant to treatment with conventional agents. Optimal therapeutic responses to clozapine have been reported with serum concentrations between 350 microg/L and 1000 microg/L. Cl...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920007780655469
更新日期:2007-05-01 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:BACKGROUND:Colorectal cancer is the third important cause of cancer-associated deaths across the world. Hence, there is an urgent need for understanding the complete mechanism associated with colorectal cancer, which in turn can be utilized toward early detection as well as the treatment of colorectal cancer in humans....
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200220666191007153238
更新日期:2019-01-01 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::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::Maternal antenatal therapy with glucocorticoids (GC) is routinely used to prevent lung immaturity. The potential harmful effects on other organs, including in particular the central nervous system (CNS), are still controversial. In the present review we aimed to investigate: i) the beneficial and detrimental effects o...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:
更新日期:2013-02-01 00:00:00
abstract:AIMS:Because of the high affinity of these animal neurotoxin proteins for some special target site, they were usually used as pharmacological tools and therapeutic agents in medicine to gain deep insights into the function of the nervous system. BACKGROUND AND OBJECTIVE:The animal neurotoxin proteins are one of the mo...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666200520090555
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:The use of psychoactive substances is one of the most dangerous social problems worldwide. Nicotine dependence results from the interaction between neurobiological, environmental and genetic factors. Serotonin is a neurotransmitter that has a wide range of central nervous system activities. The serotonin tra...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666200620201348
更新日期:2020-01-01 00:00:00
abstract::Cytochromes P450 of the liver are involved in maintenance of lipid homeostasis (cholesterol, vitamin D, oxysterol and bile acid metabolism) and in detoxification processes of endogenous compounds (i. e. bile acids) and xenochemicals (drugs). This review describes the roles of various CYPs in production of cholesterol ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920011795016890
更新日期:2011-02-01 00:00:00
abstract::The present study was designed to investigate the hepatic disposition of the prodrug AM365 and the generated antiviral guanosine analogue, AM188 in the isolated perfused rat liver (IPL). The livers of rats (n=12) were isolated and perfused with Krebs-Henseleit pH 7.4 buffer to which AM365 was added as a bolus to achie...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920005774330611
更新日期:2005-10-01 00:00:00
abstract::In the recent decades, the use of herbal products has been rapidly growing in the Western countries. While their use in many cases causes adverse effects, to date, safety issues of herbal products have not been adequately addressed. It is rarely determined whether the non-purported bioactive constituents in the herbs ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920011797470119
更新日期:2011-11-01 00:00:00
abstract::This review provides an overview of the in vitro methods currently used in studies of intestinal drug metabolism and active efflux with a special emphasis on the efflux- metabolism interplay. These methods include e.g. expressed enzymes or efflux transporters, fractionated intestinal cells, cell lines, primary cells, ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::A number of studies have appeared recently on the underlying mechanisms of liposome-cell interactions under in vitro conditions, in which isolated cell populations or cell lines were used. However, our knowledge of how liposomes interact with cells and the parameters that influence this in vivo is limited. We will sum...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200013338306
更新日期:2001-12-01 00:00:00
abstract::Glucuronidation is responsible for the clearance of a diverse range of drug and chemicals whose topology confers properties that complicate in vitro-in vivo clearance correlations as compared to those possible for oxidative metabolism. The active site of the UGTs faces the inside of the luminal space of the endoplasmi...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200023336992
更新日期:2002-12-01 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::The binding of drugs with serum proteins can affect the activity, distribution, rate of excretion, and toxicity of pharmaceutical agents in the body. One tool that can be used to quickly analyze and characterize these interactions is high-performance affinity chromatography (HPAC). This review shows how HPAC can be us...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920011795202938
更新日期:2011-05-01 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:BACKGROUND:Thiopurine antimetabolites are important agents for the treatment of severe diseases, such as acute lymphoblastic leukemia and inflammatory bowel disease. Their pharmacological actions depend on biotransformation into active thioguanine-nucleotides; intracellular metabolism is mediated by enzymes of the salv...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200217666160303104153
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Increasing incidences of type 2 diabetes make it necessary to have a better understanding of the risk factors for its prediction. Taking a note of resilience in risk factors, dynamics of the emerging factors other than traditional ones are showing a great interest in recent years which imprints a significant...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666180628170431
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Neuropsychiatric diseases primarily characterized by dementia stand third in the global list of diseases causing disability. The poor water solubility, erratic oral absorption, low bioavailability, poor intestinal absorption, and the impeding action of the blood-brain barrier (BBB) are the major factors limi...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1573399816666200627214129
更新日期:2020-01-01 00:00:00
abstract::The pressing need for targeting, detecting, monitoring, and treating diseased cells concomitantly gives rise to multi-functional nanomedicines, especially those that can combine diagnostic and therapeutic abilities, which are referred to as nanotheranostics. Recently, nanotheranostics are of significant clinical inter...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200211314060003
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:Various transporters, including efflux transporters and uptake transporters, play an important role in the pharmacokinetics of drugs. Currently, studies suggest that several antibiotics also serve as substrates for transporters. In addition, these antibiotics are usually combined with other drugs to treat di...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200217666160629114449
更新日期:2016-01-01 00:00:00
abstract::The occurrence of idiosyncratic adverse drug reactions during late clinical trials or after a drug has been released can lead to a severe restriction in its use and even in its withdrawal. Metabolic activation of relatively inert functional groups to reactive electrophilic intermediates is considered to be an obligato...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200054021799
更新日期:2005-06-01 00:00:00
abstract::With the recent advancement in nanoscience and nanotechnology, there is a growing demand for assessment of the toxicological effects of nano materials to humans and other biological systems. And a predictive toxicology approach that uses in vitro screening assays in conjunction with in vivo study results are widely em...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200216666151015113720
更新日期:2015-01-01 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