Abstract:
:Human alpha(1)-acid glycoprotein (AGP), a major carrier of many basic drugs in circulation, consists of at least two genetic variants, namely A and F1*S variant. Interestingly, the variants of AGP have different drug-binding properties. The purpose of this study was to identify the amino acid residues that are responsible for the selectivity of drug binding to genetic variants of AGP using site-directed mutagenesis. First, we screened amino acid residues in the region proximal to position 100 that are involved in binding of warfarin and dipyridamole, which are F1*S-specific ligands, and of propafenone, which is an A-specific ligand, using ultrafiltration. In the F1*S variant, His97, His100, and Trp122 were involved in either warfarin- or dipyridamole-binding, while Glu92, His100, and Trp122 participated in the binding of propafenone in the A variant. Exchange of the residue at position 92 between AGP variants reversed the relative strength of propafenone binding to the two variants, but had a markedly different effect on binding of warfarin and dipyridamole. These findings indicate that the amino acid residue at position 92 plays a significant role in drug-binding selectivity in AGP variants, especially for drugs that preferentially bind to the A variant.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Nishi K,Ueno M,Murakami Y,Fukunaga N,Akuta T,Kadowaki D,Watanabe H,Suenaga A,Maruyama T,Otagiri Mdoi
10.1002/jps.21697subject
Has Abstractpub_date
2009-11-01 00:00:00pages
4316-26issue
11eissn
0022-3549issn
1520-6017pii
S0022-3549(15)32923-3journal_volume
98pub_type
杂志文章abstract::Evaluation of a multiplexed capillary electrophoresis (CE) method for pK(a) measurements of organic compounds, including low solubility compounds, is presented. The method is validated on a set of 105 diverse compounds, mostly drugs, and results are compared to literature values obtained from multiple references. Two ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21287
更新日期:2008-07-01 00:00:00
abstract::The purpose of the present study was to clarify the expression levels of transporter proteins in human lung tissue and to analyze regional and interindividual differences in primary cultured epithelial cells. Organic cation/carnitine tranporter 1 (OCTN1) protein expression was highest (2.08 ± 1.19 fmol/μg protein) in ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23606
更新日期:2013-09-01 00:00:00
abstract::Numerous studies have demonstrated that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) increases small intestinal permeability, and this has been suggested to be a prerequisite to enteropathy. It is believed that the inhibitory effect of chiral NSAIDs on the synthesis of prostaglandins and hence t...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js960276y
更新日期:1996-11-01 00:00:00
abstract::Effects of the commercial drug zanamivir (Relenza) covalently attached to poly-l-glutamine on the infectivity of influenza A viruses are examined using the plaque reduction assay and binding affinity to viral neuraminidase (NA). These multivalent drug conjugates exhibit (i) up to a 20,000-fold improvement in anti-infl...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.22338
更新日期:2011-03-01 00:00:00
abstract::As part of a study to examine cocaine disposition and interaction with ethanol, it was necessary to characterize various properties of cocaine in the blood of the experimental animal. All studies were conducted using blood from healthy adult male Sprague-Dawley rats. Cocaine was incubated in whole blood at 37 degrees ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js960026h
更新日期:1996-06-01 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::Molecular interactions between iodine and disulfiram, clomethiazole, and tolnaftate were investigated by electron spectroscopy. Iodine forms charge transfer complexes with these molecules, with 1:1 stoichiometry and of the n-sigma type. The formation constants were compared with those obtained with antithyroid molecul...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600731205
更新日期:1984-12-01 00:00:00
abstract::In many manufacturing and research areas, the ability to accurately monitor and characterize nanoparticles is becoming increasingly important. Nanoparticle tracking analysis is rapidly becoming a standard method for this characterization, yet several key factors in data acquisition and analysis may affect results. Nan...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2016.02.005
更新日期:2016-04-01 00:00:00
abstract::The ability to successfully formulate and manufacture therapeutic protein dosage forms requires a thorough understanding of their physico-chemical properties. Proteins are inherently dynamic molecules of marginal stability. These properties present unique challenges to the pharmaceutical scientist attempting to develo...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,评审
doi:10.1002/jps.21269
更新日期:2008-09-01 00:00:00
abstract::The present work shows that the heated carbamazepine (CBZ) powder form III can be described as purely triclinic form I or a mixture of triclinic form I and monoclinic form III, depending on the resolution of the X-ray diffraction equipment used. Visual identification of the minor phase is possible when high-resolution...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.22482
更新日期:2011-07-01 00:00:00
abstract::Apparent acidity constants obtained for various benzothiadiazine diuretics by semiaqueous potentiometric titrations gave satisfactory agreement with many values obtained by aqueous potentiometry. One suitable method for determining the acidity constants of sparingly soluble drugs, the solubility variation with pH tech...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600700324
更新日期:1981-03-01 00:00:00
abstract::Aqueous solutions of several ionizable substances were stored in plastic infusion bags and the sorption of the substances monitored with time. The substances used were p-nitrophenol, p-toluidine, warfarin sodium [3-(alpha-acetonylbenzyl)-4-hydroxycoumarin sodium salt] and trifluoperazine hydrochloride (10-[3-(4-methyl...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600750608
更新日期:1986-06-01 00:00:00
abstract::A novel process based on solvent extraction was developed to produce drug-loaded polyanhydride microspheres for controlled-release applications. The technique consists of adding a chloroform solution of polyanhydride and drug into a stirred silicone oil phase containing suspended droplets of surfactant. No chemical re...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600770811
更新日期:1988-08-01 00:00:00
abstract::The new concept developed in this study is the design of poly(ethylene glycol) (PEG)-coated biodegradable nanoparticles coupled to folic acid to target the folate-binding protein; this molecule is the soluble form of the folate receptor that is overexpressed on the surface of many tumoral cells. For this purpose, a no...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/1520-6017(200011)89:11<1452::aid-jps8>3.0.
更新日期:2000-11-01 00:00:00
abstract::Two types of drug release mechanisms-matrix controlled (Q - t1/2 relationship) and partition controlled (Q - t relationship)-were reported previously. The dependency of the transition between these two processes on the solution solubility of drug is now analyzed. Mathematical expressions are derived to treat the syste...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600641011
更新日期:1975-10-01 00:00:00
abstract::The distribution of zidovudine (AZT) between plasma, brain extracellular fluid (ECF), and cerebrospinal fluid (CSF) was investigated in a crossover design study (n = 5) in unanesthetized rabbits. Drug was administered by intravenous (iv) and intracerebroventricular (icv) infusions at the same infusion rate (1.5 mg/h.k...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600840717
更新日期:1995-07-01 00:00:00
abstract::The disposition kinetics of nicotine and cotinine enantiomers was determined in rabbits. The clearance of (R)-nicotine was similar to that of (S)-nicotine, but clearance of (R)-cotinine was twice that of (S)-cotinine. Fractional conversions of both enantiomers of nicotine to cotinine were approximately 50%. These resu...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600770508
更新日期:1988-05-01 00:00:00
abstract::Regular insulin, NPH insulin, glargine insulin, calcitonin, and human growth hormone were administered to rats nasally with 0.125% tetradecyl-beta-D-maltoside (TDM), or at various times after TDM treatment. Absorption of all five peptides was enhanced initially and diminished in a time-dependent manner as the interval...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21977
更新日期:2010-04-01 00:00:00
abstract::Eighteen healthy adult volunteers completed an open-label, four-way crossover study designed to determine the bioequivalency of 160-mg cibenzoline [2-(2,2-diphenylcyclopropyl)-4,5-dihydro-1H-imidazole] capsules and tablets, their relative bioavailability compared with an oral solution of the drug, as well as the absol...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600750915
更新日期:1986-09-01 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::A rapid, simple, and accurate high-performance liquid chromatographic procedure using an amino-bonded microparticulate column is reported for the determination of chlorpromazine hydrochloride (I) and its two oxidation products, the sulfoxide (II) and the sulfone (III), in commercially available pharmaceutical dosage p...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600690217
更新日期:1980-02-01 00:00:00
abstract::The influence of different types of absorbents on moisture transmission through free (cast films) and applied (coated tablets) polymer films was investigated. In free film studies, lubricated granulations were considered to be the absorbent. The compressed tablet was considered to be the absorbent in applied film stud...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600650411
更新日期:1976-04-01 00:00:00
abstract::Some coated aspirin tablet formulations were evaluated by relating their properties to disintegrating force development patterns. The treatment of disintegrating force-time curves was effected using the Weibull distribution as proposed for dissolution. Such parameters as the maximum disintegrating force developed, the...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600730531
更新日期:1984-05-01 00:00:00
abstract::A GLC assay to quantitate the methaqualone metabolite 2-methyl-3-(2-hydroxymethylphenyl)-4(3H)-quinazolinone was developed. Standard curves were linear, and recovery of the metabolite from tissue homogenates averaged 89%. In vitro metabolism of methaqualone by the 10,000Xg supernatant fraction of rat liver homogenate ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600671114
更新日期:1978-11-01 00:00:00
abstract::The major objective of this study was to investigate and characterize the solution properties of cromolyn sodium (in D(2)O or D(2)O/H(2)O phosphate buffer at pH 7.5) using nuclear magnetic resonance (NMR) spectroscopy. The self-association of cromolyn molecules was examined primarily via one-dimensional (1)H and (13)C...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20034
更新日期:2004-05-01 00:00:00
abstract::In the present study, the interaction between phenobarbital and activated carbons which is driven by hydrophobic bonding was evaluated. The Two-Mechanism Langmuir-Like Equation was proposed to describe the isotherms for phenobarbital adsorbing to activated carbons. The parameters in the Two-Mechanism Langmuir-Like Equ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2018.06.018
更新日期:2019-01-01 00:00:00
abstract::2 closely related prostaglandins (PGs), A2 and B2, were separated by ion-exchange liquid chromatography. PGA2 and PGB2 are an isomeric pair of PGs which show little resolution on thin-layer chromatography; the pair can be resolved as gas-liquid chromatography, but use of this method requires protection of the C9-carb...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600630536
更新日期:1974-05-01 00:00:00
abstract::A rapid, sensitive, and accurate reversed-phase HPLC method has been developed for the analysis and quantification of pharmaceutical formulations containing tyrothricin (1), an antibiotic used in antiseptic buccal compressed tablets for local application. The assay has been carried out under isocratic conditions, usin...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600830815
更新日期:1994-08-01 00:00:00
abstract::Gepirone hydrochloride, an investigational anxiolytic drug, was found to have at least three polymorphic forms which melted at 180 degrees C (I), 212 degrees C (II), and 200 degrees C (III). Thermal analytical studies showed that forms I and II were an enantiotropic pair, as were forms I and III. Form III was monotrop...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600741004
更新日期:1985-10-01 00:00:00
abstract::Near-infrared spectroscopy was used to monitor the phase conversion for two solvatomorphs of caffeine, an anhydrous form and a nonstoichiometric hydrate, as a function of time, temperature, and relative humidity. The transformation kinetics between these caffeine forms was determined to increase with temperature. The ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20941
更新日期:2007-05-01 00:00:00