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, intestinal segments and other tissue preparations. Pharmacokinetics of effluxmetabolism interplay is often very complicated, possibly involving saturation, stimulation and/or inhibition of one or both of these mechanisms. Parent drug and/or metabolite(s) can be substrates for several enzymes and/or efflux proteins. These detoxifying proteins may alter the exposure of drugs to each other and, consequently, their contributions to the overall drug elimination. Depending on the complexity of the in vitro system used, different kinds of information can be extracted from the results. Simple methods concentrating on single mechanisms provide easily interpretable information, but neglect the interplay between various mechanisms influencing the kinetics in a whole organism. More complex experimental systems mimic the mechanistic complexity of in vivo setting better, but at the same time the interpretation and utilization of the results becomes more challenging. Advantages and limitations of various in vitro systems are addressed and consideration is given to the physiological relevance of the results obtained and there is discussion of approaches for in vitro - in vivo translation of the data.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Siissalo S,Heikkinen ATsubject
Has Abstractpub_date
2013-01-01 00:00:00pages
102-11issue
1eissn
1389-2002issn
1875-5453pii
CDM-EPUB-20120409-005journal_volume
14pub_type
杂志文章,评审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:BACKGROUND:The prolonged circulation time of nanoparticles in the blood is a prerequisite to realize a controlled and targeted (passive or active targeting) release of the encapsulated gene/drug at the desired site of action. The most popular method to mask or camouflage nanoparticles is the adsorbed, grafted or conjug...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666171207120643
更新日期:2018-01-01 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::Pharmacokinetic studies conducted in patients with CRF demonstrate that the nonrenal clearance of multiple drugs is reduced. Although the mechanism by which this occurs is unclear, several studies have shown that CRF affects the metabolism of drugs by inhibiting key enzymatic systems in the liver, intestine and kidney...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200033489532
更新日期:2003-04-01 00:00:00
abstract::Ageing is characterized by a progressive decline in the functional reserve of multiple organs and systems, which can influence drug disposition. In addition, comorbidity and polypharmacy are highly prevalent in the elderly. As ageing is associated with some reduction in first-pass metabolism, bioavailability of a few ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920011796504527
更新日期:2011-09-01 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::Advances in high-throughput technologies to measure genome-scale changes of genes, proteins, and other biomolecular components ('omics') in complex biological systems have dramatically revolutionized biomedical research. However, the benefits of utilizing omics information in drug development have not yet been fully r...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008786927802
更新日期:2008-12-01 00:00:00
abstract::Phenolic compounds are commonly found in natural sources like plant-based foods and beverages. These compounds have received much attention due to their unique biological properties. Polyphenols possess a significant binding affinity for serum albumins which are known to be principal extracellular proteins with a high...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200211314040009
更新日期:2013-05-01 00:00:00
abstract::Understanding the mechanism of action of organophosphates (OP)/nerve agents -- irreversible acetylcholinesterase (AChE, EC 3.1.1.7) inhibition at the cholinergic synapses followed by metabolic dysbalance of the organism -- two therapeutic principles for antidotal treatment are derived. The main drugs are anticholinerg...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920007782798144
更新日期:2007-12-01 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::The assessment of in vitro inhibition and induction of the cytochrome P450 enzymes of the liver is a critical part of the drug discovery and development process in order to ensure that two or more drugs can be safely coadministered without alterations in exposure. Early assessment of potential candidates using high th...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008786485128
更新日期:2008-11-01 00:00:00
abstract::The possibility to treat central nervous system (CNS) disorders is strongly limited by the poor access of many therapeutic agent to the target tissues. This is mainly due to the presence of the blood-brain barrier (BBB), formed by a complex interplay of endothelial cells, astrocyte and pericytes, through which only se...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920012798356943
更新日期:2012-01-01 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::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::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::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::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::There are several clinically useful endoperoxides, mainly artemisinin derivatives available in market for the treatment of malaria. These are highly potent drugs, with fastest parasite reduction ratio, broadest parasite stage specificity and effectiveness against all species of plasmodium in human. Endoperoxides are c...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920009787846323
更新日期:2009-03-01 00:00:00
abstract::This paper reviews the metabolism of new designer drugs of abuse that have emerged on the black market during the last years and is an update of a review published in 2005. The presented review contains data concerning the so-called 2C compounds (phenethylamine type) such as 4-bromo-2,5-dimethoxy-beta-phenethylamine (...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920010791526042
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND:Malignant tumors are the leading cause of death in humans. Due to the tedious efforts and investigations made in the field of marine drug discovery, there is now a scientific bridge between marine and pharmaceutical sciences. However, currently only few marine drugs have been lined towards anticancer directi...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200218666170221105402
更新日期:2018-01-01 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::With the advances in recombinant DNA biotechnology, molecular biology and immunology, the number of biotech drugs, including peptides, proteins and monoclonal antibodies, available for clinical use has dramatically increased in recent years. Although pharmacokinetic principles are equally applicable to the large molec...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920009789895499
更新日期:2009-09-01 00:00:00
abstract::Early understanding of the metabolic pathway and potential interaction of new drug candidates with other drugs is one of the goals of preclinical studies in the drug discovery process. Although other body organs are involved in drug biotransformation, the liver is the predominant organ of metabolism for a wide range o...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920012798918426
更新日期:2012-02-01 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::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::In vitro models of the liver using isolated primary hepatocytes have been used as screens for measuring the metabolism, toxicity and efficacy of xenobiotics, for studying hepatocyte proliferation, and as bioartificial liver support systems. Yet, primary isolated hepatocytes rapidly lose liver specific functions when m...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920005774832632
更新日期:2005-12-01 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::Human genome sequencing highlights the involvement of genetic variation towards differential risk of human diseases, presence of different phenotypes, and response to pharmacological elements. This brings the field of personalized medicine to forefront in the era of modern health care. Numerous recent approaches have ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200217666160804150959
更新日期:2016-01-01 00:00:00
abstract::One of the major advances in the recent history of the treatment of HIV infections has been the development of different classes of effective antiretroviral drugs. In particular, the reverse transcriptase (RT) inhibitors still represent the majority of the clinically used anti-HIV drugs and constitute the main backbon...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200043335504
更新日期:2004-08-01 00:00:00