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 for a study to integrate the reported outcomes and utilize them to achieve a better understanding. Herein, efficacy and safety aspects of opioids used to manage osteoarthritic pain were assessed and compared using a model-based meta-analysis (MBMA). METHODS:To perform the analysis, a comprehensive database consisting of pain relief compounds with information on summary-level of efficacy over time, adverse events and dropout rates was compiled from multiple sources. MBMA was conducted using a nonlinear mixed-effects modeling approach. RESULTS:The results of primary efficacy endpoint analysis indicated that the doses of oxycodone, oxymorphone, and tramadol required to produce 50% of the maximum effect were 47, 84, and 247 mg per day, respectively. Efficacytime course analysis showed that opioids had rapid time to efficacy onset, suggesting potentially powerful painrelieving effects. It was also found that gastrointestinal adverse events were the most opioid-associated and dosedependent adverse effects. In addition, the analysis revealed that opioids were well-tolerated at low to moderate doses. CONCLUSION:This MBMA provides clinically meaningful insights into the efficacy and safety profiles of oxycodone, oxymorphone, and tramadol. Resultantly, the presented framework analysis can have an impact in the clinic on drug development where it can guide: the optimization of doses of opioids required to manage osteoarthritic pain; the making of precise key decisions for the positioning of new drugs, and; the design of more efficient trials.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Alhaj-Suliman SO,Milavetz G,Salem AKdoi
10.2174/1389200221666200514130441subject
Has Abstractpub_date
2020-01-01 00:00:00pages
390-399issue
5eissn
1389-2002issn
1875-5453pii
CDM-EPUB-106629journal_volume
21pub_type
meta分析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:It is well known that ethanol can cause significant morbidity and mortality, and much of the related toxic effects can be explained by its metabolic profile. OBJECTIVE:This work performs a complete review of the metabolism of ethanol focusing on both major and minor metabolites. METHOD:An exhaustive litera...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200217666160125113806
更新日期:2016-01-01 00:00:00
abstract::Bioavailability of orally administered drugs can be influenced by a number of factors including release from the formulation, dissolution, stability in the gastrointestinal (GI) environment, permeability through the gut wall and first-pass gut wall and hepatic metabolism. Although there are various enzymes in the gut ...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920010794328913
更新日期:2010-11-01 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::Thiopurines such as azathioprine, 6-mercaptopurine and 6-thioguanine are antimetabolites that have been used for several decades in the treatment of several diseases including inflammatory bowel diseases. Additional anti-inflammatory properties of these thiopurines have been discovered in recent years. Thiopurine meta...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920009790711887
更新日期:2009-11-01 00:00:00
abstract:BACKGROUND:Clinical studies during pregnancy are rare due to ethical and practical limitations. Giving pregnant females the same dosing regimen used in adult males or nonpregnant females is inappropriate. Pregnancy physiologically-based pharmacokinetic modeling is a powerful tool that can be used to refine pharmacother...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666180702104034
更新日期:2018-01-01 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::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::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: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::The pharmacological effects of a drug are highly dependent on the absorption, metabolism, elimination, and distribution of the drug. In the past few years it has become apparent that transport proteins play a major role in regulating the distribution, elimination and metabolism of some drugs. As a consequence of our n...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200023337559
更新日期:2002-06-01 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::Since conventional therapeutic approaches in cancer are highly invasive they hardly prolong patient survival for more than few months. Having the ability to stimulate both cellular and humoural immune responses, immunisation with naked plasmid DNA encoding tumour-associated antigens or tumour-specific antigens has rec...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200211314030004
更新日期:2013-03-01 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::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::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::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::This review focuses on identification of the important active site residues of CYP2D6 in terms of CYP2D6 polymorphism. A meta-analysis was performed on the reported literature regarding (1) values of the Michaelis-Menten constant (K(m)), maximal velocity (V(max)), and intrinsic clearance (V(max)/K(m)) for 41 metabolic...
journal_title:Current drug metabolism
pub_type: 杂志文章,meta分析,评审
doi:10.2174/138920011795495286
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Nanoparticles (NPs) are being used extensively owing to their increased surface area, targeted delivery and enhanced retention. NPs have the potential to be used in many disease conditions. Despite widespread use, their toxicity and clinical safety still remain a major concern. OBJECTIVE:The purpose of this...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200221666200103091753
更新日期:2019-01-01 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::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: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:BACKGROUND:Nobel laureate Sir James Black's molecule, propranolol, still has broad potential in cardiovascular diseases, infantile haemangiomas and anxiety. A comprehensive and systematic review of the literature for the summarization of pharmacokinetic parameters would be effective to explore the new safe uses of prop...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666200414094644
更新日期:2020-01-01 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:BACKGROUND:Mutation in the B RAF at V600E has been well implicated in the carcinogenesis that makes it as an attractive therapeutictarget. In the present study, we sought to identify the basis of V600E mutation at functional and structural grounds. The study also endeavors in identification of small molecule as a poten...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200218666170503114611
更新日期:2017-07-21 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::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::When used at a high dose, many anticancer drugs produce undesirable side effects including hepatotoxicity. Transdermal delivery bypasses first-pass metabolism, allowing the use of a lower dose of drug while decreasing systemic toxicity. In this review, we summarize various advanced technologies for improving anticance...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008785821693
更新日期:2008-09-01 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