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-physiologic buffers, and hydrodynamics conditions, and can not accurately perform continuous, dynamic in vivo pharmacokinetics (PK) behaviors. Therefore, different angles of GI physiology information are incorporate into novel models to forecast the dissolution and permeation of drug solid dosage forms. This review, in general, discusses some related studies of physiologically-based mechanical models to predict human absorption following oral administration in four sections. First the GIT, taken out of a complex physiological environment, where the drug is absorbed, distributed, metabolized and excreted (ADME) in the human body, is considered as the physiological basis for active pharmaceutics ingredients (API) dissolved and permeated through the epithelial cell. The second part embodies the theoretical foundation of in vitro models to predict human absorption and the corresponding in vitro.in vivo correlations (IVIVC). The third section summarizes physiologically based dissolution models developed recently, ranging from dynamic compartmental dissolution models, to biorelevant dissolution models based on certain physiological factors, to biphasic dissolution models. The last part is devoted to combined dissolution and absorption models that can be employed to simulate the continuous, dynamic behavior of oral drug delivery being dissolved and subsequently permeated across the GIT. Along with physiologically-based mechanically models spring up, pharmaceutical researchers will harvest better level A IVIVC for oral drug delivery systems, especially for sustained and controlled release preparations. On the other way hand, it will successively promote more effective bionic models to optimize prescription, design formulation, and develop innovative products.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Li Z,He Xdoi
10.2174/1389200216666150812123836subject
Has Abstractpub_date
2015-01-01 00:00:00pages
777-806issue
9eissn
1389-2002issn
1875-5453pii
CDM-EPUB-69458journal_volume
16pub_type
杂志文章,评审abstract::Evaluation and optimization of drug metabolism and pharmacokinetic data plays an important role in drug discovery and development and several reliable in vitro ADME models are available. Recently higher throughput in vitro ADME screening facilities have been established in order to be able to evaluate an appreciable f...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008786485092
更新日期:2008-11-01 00:00:00
abstract::Hepatotoxicity related to antidepressive pharmacotherapy is a major safety concern, particularly considering that severe forms of hepatic failure with fatal outcome have been reported. Severe hepatotoxic adverse drug reactions were also reported for agomelatine (AGM), an antidepressive agent, which was approved for th...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200215666140926155041
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Despite recent therapeutic advances, osteoarthritis continues to be a challenging health problem, especially in the elderly population. Opioids, which are potent analgesics, have shown an extraordinary ability to reduce intense pain in many osteoarthritic clinical trials; however, there is an increased need ...
journal_title:Current drug metabolism
pub_type: meta分析
doi:10.2174/1389200221666200514130441
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Gold nanoparticles have been exploited for nanobiotechnology applications for the last two decades. New insights of the nanomaterials as promising agent for cancer diagnosis and therapy have just started to emerge. Due to the size- and shape-dependent optical, electrical and thermal properties, gold nanopart...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200218666170925122513
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:ET-26 hydrochloride is a novel intravenous anesthetic, approved for clinical trials, that produces a desirable sedative-hypnotic effect with stable myocardial performance and mild adrenocortical suppression in rats and beagle dogs. The objective of this study was to assess the absorption, distribution, metab...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666191223105504
更新日期:2019-01-01 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:BACKGROUND:Acute Kidney Injury (AKI) is a sudden decrease in kidney function. In the early period, the highest percentage of AKI occurs among newborns hospitalized in the neonatal intensive care units, especially premature neonates. The prognosis of AKI depends on the type and severity of the cause of an injury, the ac...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200220666190321142417
更新日期:2019-01-01 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::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::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::Work on human immortalized cell lines is not considered research on human subjects, but does involve biohazards. It has also been estimated that about 80% of human cell lines are the kind of cells that they are expected. Cells that are cultured directly from a subject are referred to as primary cells. Clonetics is the...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920008783884768
更新日期:2008-03-01 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: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::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::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::Vasopressin (AVP) and its receptors play a pivotal role in maintaining body homeostasis under physiological and pathophysiological conditions. As a consequence, the vasopressin system has emerged as an important target for both diagnostic and therapeutic applications in a number of medical conditions. Stoichiometric g...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200218666170119145900
更新日期:2017-01-01 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:BACKGROUND:Drug-metabolizing enzymes and transporters play key roles in drug disposition and drug interactions. The alterations of their expression will influence drug pharmacokinetics and pharmacodynamics. However, the changes in the expression of enzymes and transporters in the disease state are still unclear. OBJEC...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666200512113731
更新日期:2020-01-01 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:: ...
journal_title:Current drug metabolism
pub_type: 社论
doi:10.2174/138920021914181211113837
更新日期:2018-01-01 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::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::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:BACKGROUND:Overactive bladder syndrome is a broadly occurring urological disorder with a distressing impact on the quality of life. The commonly used antimuscarinic drugs show poor patient compliance because of unsatisfactory potency, tolerability and high occurrence of adverse effects such as dry mouth, blurred vision...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200221666200425211139
更新日期:2020-01-01 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::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::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::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::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::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