Abstract：
:The effect of variable protein binding (taken as independent parameter) on pharmacological activity of drugs is considered in terms of the exposure or the steady state concentration of unbound drug at targeted tissue. Based on the application of the parallel tube or dispersion models it is shown that for the most common case of orally administered drugs eliminated mainly by hepatic metabolism the increase of protein binding may be beneficial for drug action. In contrary, consideration of this case using the well-stirred model suggests that changes in protein binding do not influence drug efficiency. The relatively simplistic well-stirred model appears not accurate enough to reveal the influence of variation in protein binding on drug exposure. The conclusion in favor of the predictions based on parallel tube or dispersion models is supported by experimental data. In case of the oral dosing of drugs that are subjected to nonhepatic elimination as well as for parenteral drug administration with arbitrary routes of elimination the decrease in protein binding would lead to the increase of unbound drug exposure and thus may enhance drug efficiency. An advanced approach to evaluation of drug activity based on the assumption of the necessity to exceed certain minimal drug concentration at action site is implied. Such a consideration leads to the conclusion that there should be an optimal value of protein binding which provides maximum drug activity. The case when drug action is determined by binding to targeted receptors is discussed in terms of equilibrium binding and kinetics.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Berezhkovskiy LMdoi
10.1002/jps.21958subject
Has Abstractpub_date
2010-04-01 00:00:00pages
2153-65issue
4eissn
0022-3549issn
1520-6017pii
S0022-3549(16)30497-Xjournal_volume
99pub_type
杂志文章abstract：:Profiles of the steady-state concentrations of haloperidol (HL) and its major metabolite, reduced haloperidol (RHL), in plasma versus time were determined in 10 Japanese patients whose schizophrenic symptoms were clinically controlled by fixed, oral maintenance doses (4-30 mg/day, three times a day) for greater than 4...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600811010
更新日期：1992-10-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js970301f
更新日期：1998-04-01 00:00:00
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doi：10.1002/jps.2600720108
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600800310
更新日期：1991-03-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
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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
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doi：10.1002/jps.2600770811
更新日期：1988-08-01 00:00:00
abstract：:A semi-automated protein binding assay using equilibrium dialysis (ED) and a novel mixed-matrix methodology has been developed. This method decreases mass spectrometer run time and reduces the likelihood of experimental artifacts. In this cassette-based approach, a single matrix is prepared following dialysis by mixin...
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doi：10.1002/jps.22188
更新日期：2010-12-01 00:00:00
abstract：:Hemoglobin microcapsules were prepared through cross-linking of hemoglobin itself with various acyldichlorides. Variations in the reticulation conditions were preformed in order to ameliorate the oxygen dissociation curve, the mean diameter, and the possibility for the microcapsules to be lyophilized. With terephthalo...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600710710
更新日期：1982-07-01 00:00:00
abstract：:A simultaneous GLC determination for methyl salicylate and menthol in a topical analgesic formulation is reported. n-Nonadecane is used as the internal standard. The method is rapid, accurate, precise, and selective in the presence of salicylic acid and ethyl salicylate. ...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600680431
更新日期：1979-04-01 00:00:00
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更新日期：1986-12-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730740
更新日期：1984-07-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.04.002
更新日期：2019-09-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23805
更新日期：2014-02-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.03.006
更新日期：2019-08-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670211
更新日期：1978-02-01 00:00:00
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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：:The effect of dimethyl sulfoxide, dimethyl formamide, and dimethyl acetamide on the basal stratum corneum of excised nude mouse skin was investigated. All of these dipolar aprotic solvents caused a swelling of the basal stratum corneum cells and a disruption of the normal keratin pattern. This behavior suggests that d...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600770106
更新日期：1988-01-01 00:00:00
abstract：:It is hypothesized that ferrocene (FC)-loaded nanocarriers (FC-NCs) are safe label-free contrast agents for cochlear biodistribution study by transmission electron microscopy (TEM). To test this hypothesis, after engineering, the poly(epsilon-caprolactone)/polyglycolide NCs are tested for stability with various types ...
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更新日期：2016-10-01 00:00:00
abstract：:During stability studies at high temperature (70 degrees C) and low relative humidity ( approximately 0%), the recovery of an asparagine containing hexapeptide (VYPNGA) and its known deamidation products from solid polyvinylpyrrolidone (PVP) matrices was incomplete. To determine the causes of this mass loss, formulati...
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更新日期：2003-03-01 00:00:00
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更新日期：2001-12-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600760807
更新日期：1987-08-01 00:00:00
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更新日期：1996-01-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.10071
更新日期：2002-03-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600700930
更新日期：1981-09-01 00:00:00
abstract：:In this work, a novel risk-based methodology for lot release is proposed. Its objective is to assess the risk that a lot declared to have passed truly meets product specifications. The methodology consists of 3 parts: adaptive sample size determination, estimation of the probability that the product was within specifi...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2019.10.011
更新日期：2020-02-01 00:00:00
abstract：:Employing the roots of Iris missouriensis, two known triterpenes, iso-iridogermanal and zeorin, were isolated and identified. As presently reported, they were found to demonstrate cytotoxic activity toward cultured P-388 cells (ED50 = 0.1 and 1.1 microgram/mL, respectively). Additionally, a new triterpene that demonst...
journal_title：Journal of pharmaceutical sciences
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更新日期：1986-03-01 00:00:00
abstract：:To explore the possibility of cyclodextrin click clusters (CCCs) as a new cyclodextrin-based excipient, we prepared three different CCCs; heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (HT-β-CD), heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}{2,3-di-O-methyl}-β-cyclodextrin (...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24107
更新日期：2014-10-01 00:00:00
abstract：:Supercritical fluid emulsion extraction is an innovative technology that uses supercritical carbon dioxide (SC-CO(2)) to extract the dispersed oily phase of an emulsion. This technology was used to produce poly-lactic-co-glycolic acid (PLGA) microspheres charged with two common NSAIDs: piroxicam (PX) and diclophenac s...
journal_title：Journal of pharmaceutical sciences
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更新日期：2010-03-01 00:00:00
