Abstract：
:The pathogenic bacterium Staphylococcus aureus can penetrate host cells. However, intracellular S. aureus is not considered during antimicrobial agent selection in clinical chemotherapy because of the lack of information about drug transportability into cells in vivo. We focused on agents used to treat methicillin-resistant S. aureus (MRSA) (vancomycin, arbekacin, linezolid, and daptomycin) and indirectly assessed the drug levels in intracellular compartment using plasma, tissue homogenates, and interstitial fluid (ISF) samples from the skin of rats using the microneedle array technique. Lower drug levels were observed in the ISF than in the plasma for daptomycin but extracellular and intracellular drug levels were comparable. In contrast, vancomycin, arbekacin, and linezolid showed higher concentrations in the ISF than in the plasma. Intracellular transport was estimated only for arbekacin. Stasis of vancomycin in the ISF was also observed. These results suggest that both low vancomycin exposure against intracellular S. aureus infection and long-term subinhibitory drug levels in the ISF contribute to the failure of treatment and emergence of antibiotic resistance. Based on its pharmacokinetic characteristics in niche extravascular tissue spaces, arbekacin may be suitable for achieving sufficient clinical outcomes for MRSA infection because the drug is widely distributed in extracellular and intracellular compartments.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Kobuchi S,Kita Y,Hiramatsu Y,Sasaki K,Uno T,Ito Y,Sakaeda Tdoi
10.1016/j.xphs.2020.09.045subject
Has Abstractpub_date
2021-02-01 00:00:00pages
898-904issue
2eissn
0022-3549issn
1520-6017pii
S0022-3549(20)30576-1journal_volume
110pub_type
杂志文章abstract：:A modification of wet agglomeration technique is developed and demonstrated by agglomerative crystallization process for a nonapeptide (ABT-510) to improve processing of needle like crystals. Our procedure involves exploiting partial miscibility of the crystallization solvent system for in situ generation of a wetting...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21063
更新日期：2008-03-01 00:00:00
abstract：:The aminoxyl (nitroxyl) labeled (2-chloroethyl)nitrosocarbamoyl (CNC) derivatives of amino acids, i.e., N-[[N'-(2-chloroethyl)-N'-nitrosoamino]carbonyl]-A-(1-oxy-2,2,6,6- tetramethylpiperidin-4-yl)amides, A = glycyl (10a), A = L-alanyl (10b), A = L-valyl (10c), A = L-phenylalanyl (10d), were synthesized and evaluated ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830715
更新日期：1994-07-01 00:00:00
abstract：:Benzydamine hydrochloride (Tantum, 1) is a photoallergic and phototoxic anti-inflammatory and analgesic agent. This drug is photolabile under aerobic and anaerobic conditions. Irradiation of a methanol solution of benzydamine under oxygen or argon at 300 nm affords 5-hydroxybenzydamine (2) and 2-beta-dimethylaminoprop...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600820407
更新日期：1993-04-01 00:00:00
abstract：:The use of second generation cationic liposomes to deliver cytotoxic drugs to solid tumors is a rational and promising therapeutic approach, given the natural affinity of cationic carrier molecules for the tumor microvasculature. Cationic liposomal therapeutics are effective in the treatment of cancers that are resist...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.21458
更新日期：2009-02-01 00:00:00
abstract：:A number of arylidene derivatives of alicyclic ketones and some corresponding oximes, oxime esters, and related compounds were prepared as candidate cytotoxic agents. All of the compounds were evaluated against murine L1210 lymphoid leukemia cells. In general, cytotoxicity was greatest with the alpha,beta-unsaturated ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830619
更新日期：1994-06-01 00:00:00
abstract：:Glycerol stabilizes cyanocob(III)alamin (vitamin B12) against anaerobic photolysis by a high-intensity UV light source or a low-intensity fluorescent light source. The likely mechanism for stabilization by viscosigens is a decrease in diffusion and an enhancement of radical-pair recombination. Glycerol (25% or greater...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600820619
更新日期：1993-06-01 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：:The organic anion-transporting polypeptide (OATP) 2B1 which is ubiquitously expressed in the human body is assumed to play an important role in the cellular uptake of many drugs. Although the expression and function of this solute carrier transporter is well characterized in the human liver and other tissues, little i...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.04.001
更新日期：2017-09-01 00:00:00
abstract：:The distribution conditions in oil-water emulsions prepared by emulsifying a 1:1 eutectic mixture of lidocaine and prilocaine with a nonionic surfactant in water were studied by membrane and gel filtration methods. In this system, the local anesthetics are considered to be freely dissolved, surfactant solubilized, and...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600741112
更新日期：1985-11-01 00:00:00
abstract：:Correlations between the bioavailability parameters for erythromycin stearate tablets from five manufacturers and in vitro tests of these tablets were examined using forward (stepwise), multiple linear regression analysis. Bioavailability parameters were determined in clinical studies employing a balanced, incomplete ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：
更新日期：1980-11-01 00:00:00
abstract：:(13)C labeling was used to enhance the sensitivity of (13)C solid-state NMR to study the effect of tabletting on the polymorphism of a steroidal drug. The steroidal drug Org OD 14 was (13)C labeled and formulated into tablets containing only 0.5-2.5% active ingredient. The tablets were subsequently studied by solid-st...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20236
更新日期：2005-02-01 00:00:00
abstract：:Griseofulvin/cyclodextrin interactions were investigated in aqueous environment and in solid state. Two cyclodextrin derivatives (beta-cyclodextrin and 2-hydroxypropyl beta-cyclodextrin) were used to prepare different physical mixtures and kneaded systems, and the drug/cyclodextrin ratios were 1:1 and 1:2 mol/mol. Sca...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js970233x
更新日期：1998-07-01 00:00:00
abstract：:The dissolution rates of the two polymorphic forms of sulfathiazole containing polyethylene glycol 4000 were significantly different in water. The effect of agitation on the dissolution rates also was studied. At higher stirring speeds, the dissolution rates of the stable form were affected more than the metastable fo...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650233
更新日期：1976-02-01 00:00:00
abstract：:The in vitro binding of warfarin by human serum albumin was studied at various temperatures and at pH 7.4 by a frontal gel filtration technique. The results can be best described in terms of a two class-of-binding site model, in which the numbers of primary and secondary sites are constrained to the average values for...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600651127
更新日期：1976-11-01 00:00:00
abstract：:Biodegradable, dextran-based ion-exchange microspheres (IE-MS) have been used for localized delivery of anticancer drugs and chemosensitizers. Because of their hydrophilic nature, the IE-MS release their payload quickly. The purpose of this work was to develop an IE-MS system that could provide a broad range of releas...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/(SICI)1520-6017(200006)89:6<807::AID-JPS13
更新日期：2000-06-01 00:00:00
abstract：:Drug-induced phototoxic skin responses involves photoirritation, photoallergy, and photogenotoxicity. In the present study, we attempted to develop effective analytical tools to predict the photogenotoxic potential of pharmaceutical substances on the basis of their photobiological and DNA-binding properties. Photoclea...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21670
更新日期：2009-10-01 00:00:00
abstract：:Water evaporation rates were measured from thin samples of a model layered structure of stratum corneum lipids with 32% water. A model with only free fatty acids present gave the lowest evaporation rates, while a model with only oleic acid gave values approximately 50% higher. Using the total lipid spectrum of stratum...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600780808
更新日期：1989-08-01 00:00:00
abstract：:A method to determine the adherence of drugs to the esophagus was developed using isolated swine esophagi. A number of types of tablets and capsules (e.g., of doxycycline) were tested. The results showed that the tendency of products to adhere to the esophagus can be regulated by pharmaceutical properties. It was conc...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600710904
更新日期：1982-09-01 00:00:00
abstract：:A crude chloroform-soluble fraction of the ethanol extract of the leaves of Bursera klugii showed activity against two test systems, the P-388 lymphocytic leukemia (3PS) and the human epidermoid carcinoma of the nasopharynx (9KB). The PS activity was due to two constituents, sapelins A and B. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660645
更新日期：1977-06-01 00:00:00
abstract：:New methods are being applied to distinguish silicone oil droplets from subvisible particles in therapeutic protein formulations. The need to standardize these methods and compare them to established methods is critical to increase the understanding of the risks from protein aggregation and other subvisible particulat...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23554
更新日期：2013-06-01 00:00:00
abstract：:The usefulness of poly(N-isopropyl acrylamide), PNIPA, for preparing sustained release matrix or photopolymerization-coated cellulosic pellets was evaluated. Theophylline pellets and granules were prepared using powdered cellulose (PC), poly(vinylpyrrolidone) (PVP), and PNIPA of Mw approximately 330 kDa, Mn approximat...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20708
更新日期：2007-01-01 00:00:00
abstract：:Preliminary studies indicate that it may be possible to differentiate the effects of a nephrotoxic substance from those of diuretic agents by the measurement of both urine and plasma osmolarity. The nephrotoxic substance, mercuric chloride, decreases urinary osmolality and increases plasma or serum osmolality. The diu...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660411
更新日期：1977-04-01 00:00:00
abstract：:Single-dose oral administration of a commercial polychlorinated biphenyl product containing 54% chlorine provided data with which to plot the time course of total polychlorinated biphenyl and individual components in the blood of swine and sheep. Pharmacokinetic parameters describing absorption from the gut and elimin...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640807
更新日期：1975-08-01 00:00:00
abstract：:For development and optimization of protein formulation sensitive analytical tools are required to follow both aggregation and changes in protein structure. The latter can be seen as the beginning of physical instability leading to aggregation. The focus of this work laid on the development of a novel analysis simulta...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22808
更新日期：2012-02-01 00:00:00
abstract：:The hydrogen-bonded interactions of chloral hydrate and halide ions have been investigated conductometrically at 25.00 degrees C in aqueous solutions. In spite of the strong competing effect of water, the 1:1 associates have relatively high stability constants, in the order of chloride greater than bromide greater tha...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600770714
更新日期：1988-07-01 00:00:00
abstract：:Pancreatic islet transplantation is a promising advanced therapy that has been used to treat patients suffering from diabetes type 1. Traditionally, pancreatic islets are infused via the portal vein, which is subsequently intended to engraft in the liver. Severe immunosuppressive treatments are necessary, however, to ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.10.028
更新日期：2020-01-01 00:00:00
abstract：:The impact of intestinal conjugative metabolism on oral bioavailability was assessed by sequential and simultaneous analyses of the reported data in humans. The data were retrieved from reports on drugs that are metabolized by sulfate conjugation, and the organ availabilities affecting oral bioavailability were differ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20269
更新日期：2005-03-01 00:00:00
abstract：:In this study, we attempted to improve the oral absorption of ceftriaxone (CTX) by using an absorption carrier and the CTX complex together. After the CTX-Ca-carrageenan gel complex was prepared, several kinds of compounds (Capmul MCM C10, Gelucire 44/14, glycyrrhizin) were screened as potential oral enhancers for our...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10563
更新日期：2004-03-01 00:00:00
abstract：:Since the discovery of liposomes or lipid vesicles derived from self-forming enclosed lipid bilayers upon hydration, liposome drug delivery systems have played a significant role in formulation of potent drugs to improve therapeutics. Currently, most of these liposome formulations are designed to reduce toxicity and t...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.1023
更新日期：2001-06-01 00:00:00
abstract：:This whitepaper highlights current challenges and opportunities associated with continuous synthesis, workup, and crystallization of active pharmaceutical ingredients (drug substances). We describe the technologies and requirements at each stage and emphasize the different considerations for developing continuous proc...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24252
更新日期：2015-03-01 00:00:00
