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 in the rat. The in vivo clearance of tanshinone IIA was acquired from a pharmacokinetic study in rat. The results show that the prediction accuracy acquired from the microsome combined with the NADPH is poor. The in vivo clearance in the rat is almost 32 fold higher than the clearance predicted in microsome. The predicted clearance of the S9 model combined with both NADPH and UDPGA system is about 4 fold lower than the in vivo clearance. The predicted clearance of the cytosol combined with the two cofactor system is about 7 fold lower than the in vivo clearance. Although the prediction accuracy acquired from the S9 and cytosol system is not perfect, the prediction accuracy is improved in these two incubation systems. Using S9 combined with both the phase I and phase II metabolism can improve the prediction accuracy.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Li P,Wang GJ,Li J,Zhang Q,Liu X,Khlentzos A,Roberts MSdoi
10.2174/138920008783331103subject
Has Abstractpub_date
2008-01-01 00:00:00pages
39-45issue
1eissn
1389-2002issn
1875-5453journal_volume
9pub_type
杂志文章abstract:BACKGROUND:The metabolic/biotransformation pathways of atypical antipsychotics (aripiprazole, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) have been characterized and reviewed. However, comparisons of excretory pathways remain unexplored. OBJECTIVE:To analyze the excretio...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920010791636202
更新日期:2010-07-01 00:00:00
abstract::Talin is an intracellular cytoskeletal protein and one of the major components of the focal adhesion complex. It mainly acts as an interlink between transmembrane integrin receptors and cytosolic F-actin. Apart from integrins and actin, it also interacts with various other proteins in the adhesion complex to regulate ...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666200214114018
更新日期:2020-01-01 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::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::Toxicogenomics is defined as an integration of genomics (transcriptomics, proteomics and metabolomics) and toxicology. It is a scientific field that studies how the genome is involved in responses to environmental stressors and toxicants. It combines studies of mRNA expression, cell and tissue-wide protein expression ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008783884696
更新日期:2008-03-01 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::Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted a lot of interest due to their widespread diagnostic and therapeutic applications in neuro-oncology. Functinalization of the particles surface with targeting molecules that recognize tumor receptors might be exploited for the specific brain tumor targe...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:
更新日期:2016-06-15 00:00:00
abstract::For the pharmaceutical industry, one of the challenges in evaluating the risk of future compound attrition at the discovery stage is the successful prediction of the major routes of clearance in humans. For compounds cleared by metabolism, such information will help to avoid the development of compounds that will exhi...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200033489235
更新日期:2003-12-01 00:00:00
abstract::Decarboxylation, reduction and hydrolysis can yield active metabolites from the parent drug. Major therapeutic indications and metabolic routes of these drugs are reviewed. Changes in the logP values (determined and calculated) from the parent drug to the active metabolite show certain characteristics in comparison to...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920012800840437
更新日期:2012-07-01 00:00:00
abstract::Gender differences in drug concentrations, drug response and toxicity have been attributed to various distinct yet interrelated physiological and molecular mechanisms. Drug transporters and metabolising enzymes play an important role in the xenobiotic cascade and are important regulators of drug disposition at the mol...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920009788498996
更新日期:2009-05-01 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::This paper reviews the empirical methods of quantitative microdialysis that have been used to interpret the results obtained from pharmacokinetic studies. The concept of extraction efficiency or recovery and the properties of recovery in vivo (variation with flow rate, time dependency and influence of the mode of admi...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200053586109
更新日期:2005-04-01 00:00:00
abstract::We present a review of recent investigations of anticancer drug bexarotene in this article. As one of the novel synthetic analogs of retinoids, bexarotene selectively binds to and activates the retinoid X receptor (RXRs) subfamilies, exerting a prophylactic and therapeutic effect on a large series of tumors in vitro a...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920021702160114121706
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Bioequivalence studies are a vital part of drug development. The average bioequivalence approach is the standard method of assessment to conclude whether the generic product is bioequivalent to the innovator product. Of late, debates are on whether the average bioequivalence approach adequately addresses dru...
journal_title:Current drug metabolism
pub_type: 杂志文章,随机对照试验
doi:10.2174/1389200221666200401105119
更新日期:2020-01-01 00:00:00
abstract::Fluoropyrimidines and oxaliplatin continued to be the mainstay of therapeutic regimens in the treatment of colorectal cancer (CRC). For this reason, pharmacokinetic and metabolism of these drugs were analyzed and the identification of accurate and validated predictive, prognostic and toxicity markers became necessary ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920011798062300
更新日期:2011-12-01 00:00:00
abstract::The combined treatment with anticonvulsant and antidepressant drugs is reported in both neurologic and psychiatric practice; it is, therefore, evident that the issue of managing such type of polytherapy is frequently encountered by clinicians. To review current literature on pharmacokinetic interactions between antico...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008786049311
更新日期:2008-10-01 00:00:00
abstract::Chronic heart failure (CHF) is now recognized as a multisystem disorder with increased sympathetic tone, hormonal derangements, an anabolic/catabolic imbalance, endothelial dysfunction, and systemic low-grade inflammation affecting various organ systems. Pro-inflammatory cytokines appear to play important roles in tha...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920009787048374
更新日期:2009-01-01 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::Recent advances in the biological and analytical sciences have led to unprecedented interest in the discovery and quantitation of endogenous molecules that serve as indicators of drug safety, mechanism of action, efficacy, and disease state progression. By allowing for improved decision-making, these indicators, refer...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920006777697918
更新日期:2006-06-01 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:The administration of multiple drugs for the treatment of diseases is an integral aspect of modern medicine. Though its purpose is to create the intended therapeutic effect, the unintended consequences of drug interactions can cause severe side effects and subsequent economic losses. Likewise, herbal extract...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200216666151103121253
更新日期:2016-01-01 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:OBJECTIVES:Induction or inhibition of cytochrome P450 (CYP) enzyme activities, enzymes that activate or detoxify xenobiotics, is one mechanism by which vegetables may alter cancer risk. As the effect of food on CYP enzyme activities have not been studied in the Jordanian population, we examined the effect of supplement...
journal_title:Current drug metabolism
pub_type: 临床试验,杂志文章
doi:10.2174/138920007779315080
更新日期:2007-01-01 00:00:00
abstract::The M2 proton channel is translated by the M gene segment of influenza viruses, and has been adopted as an attractive target for influenza A viruses, on which a series of adamantane-based drugs act. However, recently epidemic influenza viruses have had strong resistant effects against the adamantane-based drugs. In th...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200215666140605130406
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Interleukin-28B (IL28B) locus on a human chromosomal region mapped to 19q13 execute immune defense against viruses. During Hepatitis C Virus (HCV) infection the IL28B has a promising role in deciding the consequence of infection for spontaneous clearance of viruses or causing chronic liver infection. Treatme...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666180129115359
更新日期:2018-01-01 00:00:00
abstract::Personalized medicine has gained significant attention over the last decade as technologies for understanding biological differences between individuals have advanced dramatically. There are many potential benefits of personalized medicine including minimizing risk of drug toxicity, increasing benefit from drugs used,...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920012802138615
更新日期:2012-09-01 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 Cytochrome P450 4A subfamily is one of eighteen subfamilies in the CYP4 family and presently consists of twenty individual forms in nine different mammalian species. The major substrates for CYP4A forms are fatty acids, but recent studies have shown other non-fatty acid substrates may be metabolized by specific CY...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200013338423
更新日期:2001-09-01 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: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