Abstract：
:Bile acid (BA) retention within hepatocytes is an underlying mechanism of cholestatic drug-induced liver injury (DILI). We previously developed an assay using sandwich-cultured human hepatocytes (SCHHs) to evaluate drug-induced hepatocyte toxicity accompanying intracellular BA accumulation. However, due to shortcomings commonly associated with the use of primary human hepatocytes (e.g., limited availability, lot-to-lot variability, and high cost), we examined if the human hepatic stem cell line, HepaRG, might also be applicable to our assay system. Consequently, mRNA expression levels of human BA efflux and uptake transporters were lower in HepaRG cells than in SCHHs but higher than in HepG2 human hepatoma cells. Nevertheless, HepaRG cells and SCHHs showed similar toxicity responses to 22 selected drugs, including cyclosporine A (CsA). CsA (10 μM) was cytotoxic toward HepaRG cells in the presence of BAs and also reduced the biliary efflux rate of [(3)H]taurocholic acid from 38.5% to 19.2%. Therefore, HepaRG cells are useful for the evaluation of BA-dependent drug toxicity caused by biliary BA efflux inhibition. Regardless, the prediction accuracy for cholestatic DILI risk was poor for HepaRG cells versus SCHHs, suggesting that our DILI model system requires further improvements to increase the utility of HepaRG cells as a preclinical screening tool.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Susukida T,Sekine S,Nozaki M,Tokizono M,Oizumi K,Horie T,Ito Kdoi
10.1016/j.xphs.2016.01.013subject
Has Abstractpub_date
2016-04-01 00:00:00pages
1550-60issue
4eissn
0022-3549issn
1520-6017pii
S0022-3549(16)00309-9journal_volume
105pub_type
杂志文章abstract：:Intranasal delivery of flurazepam, midazolam, and triazolam was studied in a dog model as a possible alternate route of drug administration for treatment of insomnia. Four beagles received each hypnotic by both intranasal and oral routes on two separate occasions. Plasma concentrations for each hypnotic after dosing w...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600801207
更新日期：1991-12-01 00:00:00
abstract：:Aggregation of therapeutic monoclonal antibodies has a potential risk of immunogenicity, requiring minimization of aggregate formation. We have developed a fitting formula for antibody aggregation at 40°C based on physicochemical parameters, including colloidal and conformational stabilities. An IgG1 monoclonal antibo...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.10.038
更新日期：2020-01-01 00:00:00
abstract：:Chitosan microspheres were evaluated for sustained-release of recombinant human interleukin-2 (rIL-2) in this study. In addition, the effects of different formulation factors, such as chitosan and protein concentrations, the volume of sodium sulfate solution, addition technique of rIL-2, and presence of glutaraldehyde...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10122
更新日期：2002-05-01 00:00:00
abstract：:Peptide-based therapies have the potential to induce antibody formation if the molecules differ from a native human peptide. Several reports have disclosed the occurrence of antibody generation in a patient treated with exenatide. The immune response can be problematic from a clinical stand point, particularly if the ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24238
更新日期：2015-01-01 00:00:00
abstract：:Two polymorphs of celastrol were discovered and fully characterized by X-ray powder diffraction, thermogravimetry analysis, and differential scanning calorimetry. The single-crystal structures of form I and the isostructural solvate of form II were disclosed by single-crystal X-ray diffraction. The apparent solubility...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.07.008
更新日期：2018-11-01 00:00:00
abstract：:Amphiphilic cyclodextrins (CDs) are biocompatible derivatives of natural CDs and are able to form nanoparticles or polyplexes spontaneously. In this study, nanoparticles prepared from nonionic (6OCaproβCD) or cationic amphiphilic CD (PC βCDC6) were used comparatively to develop nanoparticles intended for breast cancer...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.06.021
更新日期：2016-10-01 00:00:00
abstract：:Tuberculosis (TB) is a serious infectious disease that affects more than new 10 million patients each year. Many of these cases are resistant to first-line drugs so second-line ones, like fluoroquinolones, need to be incorporated into the therapeutic. Ofloxacin (OF) is a fluoroquinolone which demonstrates high antibio...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.05.027
更新日期：2020-09-01 00:00:00
abstract：:Determination of the kinetics of water-soluble degradation products inside poly(lactide-co-glycolide) (PLGA) delivery systems during polymer degradation is important to evaluate the polymer microclimate conditions, particularly microclimate pH changes for optimization of encapsulated drug stability. A pre-derivatizati...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10524
更新日期：2004-02-01 00:00:00
abstract：:Toxin-conjugates, complexes designed from the fusion of tissue toxins and pathology-specific ligands, offer the potential for targeted cytotoxic therapy. Some have postulated that the recurrent failure of these conjugates to exhibit benefit in animal models of vascular injury arose because the timing and frequency of ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js980086i
更新日期：1998-11-01 00:00:00
abstract：:A high-performance liquid chromatographic (HPLC) method for the simultaneous determination of pralidoxime chloride (I) and its major decomposition products in an injectable formulation is described. I and its decomposition products were detected and quantitated by their UV absorbances at 270 nm, after being separated ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720710
更新日期：1983-07-01 00:00:00
abstract：:Methods are presented for the separation of tetracycline, tetracycline analogs, and their potential impurities by reversed-phase ion-pair chromatography. The mobile phase consisted of a phosphate buffer with tripropylamine or N,N-dimethyloctylamine as counterions and acetonitrile as the organic modifier. The chromatog...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600710221
更新日期：1982-02-01 00:00:00
abstract：:The aim of this study was to investigate the bioavailability enhancement of the biopharmaceutics classification system class II compound ezetimibe loaded in ordered mesoporous silica (OMS) in dogs. The OMS was characterized as highly ordered mesoporous material with a narrow pore size distribution. Ezetimibe was loade...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23016
更新日期：2012-03-01 00:00:00
abstract：:The recombinant fusion proteins hybrid 1 [H1 (Ag85B-ESAT-6)] and hybrid 56 [H56 (Ag85B-ESAT-6-Rv2660c)] derived from Mycobacterium tuberculosis are promising antigens for subunit vaccines against tuberculosis. Both antigens are early batches of antigens to be enrolled in human clinical trials and it is therefore impor...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23669
更新日期：2013-10-01 00:00:00
abstract：:The metabolic fate of aprophen hydrochloride (2-diethylaminoethyl 2,2-diphenylpropionate) was studied in rats after intravenous administration. Both 14C-labeled and unlabeled aprophen were used in these studies. Blood samples were collected and analyzed to determine the identities of the metabolites formed. Utilizing ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600770210
更新日期：1988-02-01 00:00:00
abstract：:The advisability of a progressive curtailment of organic solvent film coating offers an incentive to develop latex systems. Here, the use of aqueous colloidal dispersions of cellulose acetate, plasticized with water-soluble additives, is proposed as an alternative way to obtain cellulose acetate membranes either by ca...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600760609
更新日期：1987-06-01 00:00:00
abstract：:Nephropathic cystinosis is a rare autosomal recessive disease characterised by raised lysosomal levels of cystine in the cells of all the organs. It is treated by the 6-h oral administration of the aminothiol, cysteamine, which has an offensive taste and smell. In an attempt to reduce this frequency and improve the tr...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23246
更新日期：2012-10-01 00:00:00
abstract：:Nasal mucosa excised from dogs or rabbits was mounted as a flat sheet in an in vitro chamber. The permeability was assessed by measuring the unidirectional flux of the radiolabeled tracer compounds, water, sucrose, polyethylene glycol, and cholecystokinin octapeptide. The permeability coefficients calculated from the ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600761206
更新日期：1987-12-01 00:00:00
abstract：:The effects of five conventional film-coating materials on tablet hardness were studied. Placebos showed apparently linear increases in hardness as coatings were applied. Completely coated samples exhibited hardness increases from 50 to 140%, with a corresponding 3% increase in tablet weight. Equations were derived re...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650908
更新日期：1976-09-01 00:00:00
abstract：:The aim of this work is to determine if a stability testing protocol based on the correlations between crystallization onset and relaxation time above the glass transition temperature (T(g)) can be used to predict the crystallization onsets in amorphous pharmaceutical systems well below their T(g). This procedure assu...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22232
更新日期：2010-09-01 00:00:00
abstract：:Therapeutic use of anti-inflammatory steroids is limited due to their potential suppressive effects on pituitary-adrenal function and the immune system. Based on the antedrug concept, a new class of potent locally active compounds with reduced risk of side effects has been synthesized from prednisolone by introducing ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600790716
更新日期：1990-07-01 00:00:00
abstract：:Controlling residual solvent levels is a major concern in pharmaceutical freeze-drying from co-solvent systems. This review provides an overview of the factors influencing this process and estimates their potential to reduce residual solvents in freeze-dried products. Decreased solvent contents are potentially correla...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1016/j.xphs.2018.04.001
更新日期：2018-08-01 00:00:00
abstract：:Antibody therapeutics with poor solubility in the subcutaneous matrix may carry unintended risks when administered to patients. The objective of this work was to estimate the risk of antibodies that precipitate in vitro at neutral pH by determining the impact of poor solubility on distribution of the drug from the inj...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.01.015
更新日期：2019-06-01 00:00:00
abstract：:Several Several 10-(1-acetyl-4-arylthiosemicarbazido) phenothiazines and their corresponding cyclized 10-(2-arylimino-3-acetylamino-4-thiazolidonyl)phenothiazines were synthetized and characterized by their sharp melting points and elemental analyses. All compounds inhibited nicotinamide adenine dinucleotide (NAD)-dep...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650319
更新日期：1976-03-01 00:00:00
abstract：:Two novel series of steroidal derivatives containing various thiourea and substituted thiazoline moieties attached to the 2- or 4-position of estrone were synthesized and examined for in vitro effect on bovine pancreatic ribonuclease activity. All compounds studied exhibited a catabolic activity. The steroidal thiazol...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600721025
更新日期：1983-10-01 00:00:00
abstract：:Chloroquine (7-chloro-4-[[4-(diethylamino)-1-methylbutyl]amino]quinoline; CQ) accumulates in the insoluble fraction of rat muscle homogenates with an equilibrium distribution ratio of 7.8 L/kg. This is of a similar magnitude to muscle:plasma ratios observed in vivo. Uptake is approximately linear, even up to concentra...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600751109
更新日期：1986-11-01 00:00:00
abstract：:Phospholipids have been extensively evaluated as an anchor for both PEGylation and receptor-targeting in liposomal formulations. However, cholesterol, another important component in biomembranes, has not been fully investigated as an alternative anchor. In this study, the potential role of cholesterol for anchoring PE...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20885
更新日期：2007-09-01 00:00:00
abstract：:A new, specific, and useful approach for the analysis of benzalkonium chloride is presented. Reversed-phase high-pressure liquid chromatography is used to determine benzalkonium chloride in an ophthalmic system at the presevative level of 0.004%. Since the method separates each homolog, it can be extended to determine...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600691006
更新日期：1980-10-01 00:00:00
abstract：:The in vitro uptake study was performed using the isolated cells of human oral mucosa, buccal and the dorsum of the tongue, to investigate the mechanisms of glucose uptake. The uptake of D-glucose was much larger in cells of the dorsum of the tongue than in buccal cells and was inhibited more extensively by 2-deoxy-D-...
journal_title：Journal of pharmaceutical sciences
pub_type： 临床试验,杂志文章
doi：10.1021/js980298f
更新日期：1999-08-01 00:00:00
abstract：:The kinetic barrier against the transport of methyl and ethyl nicotinates across the water-isopropyl myristate interface has been studied as a function of temperature using a rotating diffusion cell. The temperature dependence of the interfacial transfer kinetics has enabled calculation of the thermodynamic parameters...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720212
更新日期：1983-02-01 00:00:00
abstract：:There has been a growing interest in predicting in vivo metabolic drug-drug interactions from in vitro systems. High-throughput screening methods aimed at assessing the potential of drug candidates for drug interactions are widely used in industry. However, at present, there is no consensus on methodologies that would...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.10179
更新日期：2002-09-01 00:00:00
