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 as monoclonal antibodies, cytokines (e.g. interferon, interleukine), tissue growth factors, vaccines directed against non-infectious disease targets, and gene transfer products. Chemical as well as pre-clinical development are major challenges for biologics due to their different physicochemical properties (mostly protein structure) compared to small molecules. They demonstrate much more complex pharmacokinetic behaviour, which strongly influences their pre-clinical testing strategy. Biologics are often highly species-specific in action and immunogenic in test animal species and humans. Immunogenicity of therapeutic biologics may influence their pharmacokinetic behaviour as well as pharmacodynamics and toxicity. Biologics are frequently regulated by different procedures compared to small molecules. New guidances are evolving which reflect the rapid development of new technologies in this field. Bioanalytical method development and validation is a prerequisite not exclusively for pharmacokinetic studies but for the whole pre-clinical and clinical development. Due to their unique properties, different kinds of bioanalytical assays (mass assays, activity assays, immunogenicity assays) are necessary in early development of biologics.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Baumann Adoi
10.2174/138920006774832604keywords:
subject
Has Abstractpub_date
2006-01-01 00:00:00pages
15-21issue
1eissn
1389-2002issn
1875-5453journal_volume
7pub_type
杂志文章,评审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::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::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::Membrane transporters play an important role in intestinal absorption, distribution and clearance of drugs. Additionally transporters along with enzymes regulate tissue exposures (e.g. liver, kidney and brain), which are important for safety and efficacy considerations. Early identification of transporters involved gu...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221999210101233340
更新日期:2021-01-01 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::In recent years several arylpiperazine derivatives have reached the stage of clinical application, mainly for the treatment of depression, psychosis or anxiety. Examples are the pyrimidinylpiperazine buspirone, the chlorophenylpiperazine derivatives nefazodone and trazodone, the dichlorophenylpiperazine aripiprazole a...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920007781368908
更新日期:2007-08-01 00:00:00
abstract::Currently the major research highlights of bioengineering and medical technology are directed towards development of improved diagnostic techniques to screen complex diseases. Screening requirements are to identify the cause of illnesses, monitor improvement or progression of the state of diseases such as cancer, card...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:
更新日期:2015-01-01 00:00:00
abstract::This review provides a vista of the current opportunities and remaining challenges in the area of in vitro-in vivo extrapolation, with particular emphasis on drug binding terms in predictive models, which has been the source of much controversy. Although the importance of fu(inc) (fraction unbound in in vitro incubati...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920006776359266
更新日期:2006-04-01 00:00:00
abstract::Ophthalmic drugs are delivered to ocular tissues predominantly via relatively simple formulations, such as topically dosed water-soluble drug solutions and water-insoluble drug suspensions in ointments. An ideal topical drug delivery system should possess certain desirable properties, such as good corneal and conjunct...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920007779815977
更新日期:2007-02-01 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::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::Etoposide (VP-16), a DNA topoisomerase II poison widely used as an antineoplastic agent is also known to cause leukemia. One of its major metabolic pathways involves O-demethylation to etoposide catechol (etoposide-OH) by cytochrome P450 3A4 (CYP3A4). The catechol metabolite can undergo sequential one- and two-electro...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920006779010638
更新日期:2006-12-01 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::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::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: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::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::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: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::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: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 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::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::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 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::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::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: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: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:BACKGROUND:Methotrexate (MTX) is a folate analogue with high therapeutic efficiency in the treatment of cancers and autoimmune diseases. The efficacy and toxicity of MTX may be altered by genetic polymorphisms in genes involved in MTX metabolic pathway. Personalized pharmacotherapy based on gene polymorphisms enables a...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666171227201047
更新日期:2018-01-01 00:00:00