Abstract:
PURPOSE:The objective of this study was to elucidate the different mechanisms of action of different excipients on the oxidation of Met1, Met122, Met127, and Met138 in granulocyte colony-stimulating factor (G-CSF) by using hydrogen peroxide as the oxidant. METHODS:The oxidation of Met1, Met127, and Met138 was quantified by peptide mapping analysis. The oxidation of Met122 has biphasic oxidation kinetics with a faster second phase. Therefore, the oxidation of Met122 was quantified by two different methods: peptide mapping analysis for the first phase of oxidation and direct reverse-phase HPLC for the second phase of oxidation. RESULTS:The current work reveals that the preferential excluding excipients sorbitol, sucrose, and trehalose, in the concentration range 0-30% (w/v), and the preferential binding excipients urea and guanidine hydrochloride, in the concentration range 0-0.8 M, do not affect the oxidation of methionine residues in G-CSF at pH 4.5. The chelating agents citrate and EDTA have different effects on the rates of oxidation of methionine residues in G-CSF. At low concentrations, citrate decreases the rates, while at high concentrations, citrate increases the rates. EDTA decreases the rates of oxidation of methionine residues in G-CSF, such that its effect becomes more and more as its concentration is increased from 0 to 200 mM. The efficacy of EDTA on the rates of oxidation of the four methionine residues in G-CSF follows the order Met122 > Met127 > Met138 > Met1. CONCLUSIONS:Our results indicate that EDTA can protect the methionine residues in G-CSF against oxidation induced by hydrogen peroxide. The more exposed the methionine residue is, the more difficult it is to be protected by EDTA. The mechanism may be due to the specific ion binding of EDTA to proteins.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Yin J,Chu JW,Ricci MS,Brems DN,Wang DI,Trout BLdoi
10.1007/s11095-004-9019-xsubject
Has Abstractpub_date
2005-01-01 00:00:00pages
141-7issue
1eissn
0724-8741issn
1573-904Xjournal_volume
22pub_type
杂志文章abstract::Colonic absorption of recombinant human insulin-like growth factor I (rhIGF-I) was measured in vitro using both rat and minipig colon. The permeability coefficients were 8.03 +/- 1.03 and 4.75 +/- 0.43 x 10(-8) cm sec-1 in the rat and minipig, respectively. The steady-state flux in rat colon was linearly related to th...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018999106684
更新日期:1994-02-01 00:00:00
abstract:PURPOSE:The relationship between rat intestinal permeability (Papp) of a range of hydrophilic probe molecules and probe geometry was examined. METHODS:Molecules studies included mannitol, the polyethylene glycols (PEGs) 400, 900, and 4000, the dextran conjugated dye Texas Red (MW 3000) and the polysaccharide inulin (M...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016091915733
更新日期:1996-10-01 00:00:00
abstract:PURPOSE:A mechanism-based PK-PD model was developed to predict the time course of dopamine D(2) receptor occupancy (D(2)RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. METHODS:A population approach was utilized to quantify both the pharmacokinetics and pharmacodynamics of ol...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0477-7
更新日期:2011-10-01 00:00:00
abstract:PURPOSE:The aim of the study was to investigate whether dopamine is transferred along the olfactory pathway to the brain following nasal administration to mice. METHODS:[3H]-Dopamine was administered nasally or intravenously to female mice. Brain tissue samples were excised and the radioactive content was measured. Th...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1007542618378
更新日期:2000-06-01 00:00:00
abstract::The effect of freezing on formation of soluble and insoluble aggregates of human growth hormone (hGH) was studied. The amount of soluble aggregates was affected very little by freezing regardless of the cooling rate. In contrast, the formation of insoluble aggregates (particulates), as determined by light scattering i...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015888704365
更新日期:1991-11-01 00:00:00
abstract:PURPOSE:This study was aimed to investigate the effects of a phenolic antioxidant, butylated hydroxyanisole (BHA) and its metabolite, tert-butylhydroquinone (tBHQ) on the induction of HO-1, NQO1 and Nrf2 proteins and their regulatory mechanisms in primary-cultured hepatocytes. METHODS:After exposure of BHA and tBHQ to...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9094-2
更新日期:2006-11-01 00:00:00
abstract:PURPOSE:Knowledge about the uptake mechanism and subsequent intracellular routing of non-viral gene delivery systems is important for the development of more efficient carriers. In this study we compared two established cationic polymers pDMAEMA and PEI with regard to their transfection efficiency and mechanism of cell...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9287-3
更新日期:2007-08-01 00:00:00
abstract:PURPOSE:To create poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), where a drug-encapsulating NP core is covered with polyethylene glycol (PEG) in a normal condition but exposes a cell-interactive TAT-modified surface in an environment rich in matrix metalloproteinases (MMPs). METHODS:PLGA NPs were modified w...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1039-y
更新日期:2013-08-01 00:00:00
abstract:PURPOSE:To test the hypothesis that modification of release pattern of nonsteroidal anti-inflammatory drugs (NSAIDs) formulations shifts gastrointestinal (GI) toxicity of the drugs from the upper GI region to the distal intestine. METHODS:We assessed tiaprofenic acid (TA)-induced upper and lower increased GI permeabil...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018887216098
更新日期:1999-01-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011028227155
更新日期:2001-06-01 00:00:00
abstract:PURPOSE:The aim of this work is to design new chitosan conjugates able to self-organize in aqueous solution in the form of micrometer-size platelets. When mixed with amphotericin B deoxycholate (AmB-DOC), micro-platelets act as a drug booster allowing further improvement in AmB-DOC anti-Candida albicans activity. METH...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2117-3
更新日期:2017-05-01 00:00:00
abstract:PURPOSE:Gastrointestinal deposition of nanoparticles was examined after oral administration to mice suffering from an experimental gastric ulcer model. Local drug delivery could reduce side effects and would be a distinct improvement compared to existing therapeutic approaches, e.g. in the local therapy of Helicobacter...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-009-9834-1
更新日期:2009-05-01 00:00:00
abstract:PURPOSE:The rapid oxidation of rofecoxib under alkaline conditions has been previously reported. The oxidation was reported to involve gamma-lactone ring opening to an alcohol, which further oxidized to a dicarboxyclic acid. The oxidation was suspected to be mediated by peroxy radicals. This work further investigates t...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-6947-z
更新日期:2005-10-01 00:00:00
abstract:PURPOSE:To address the problem of precipitation of a poorly soluble drug during dissolution of highly soluble cocrystals by preparing granules intimately mixed with a water-soluble polymer. METHODS:Effectiveness of polymers as precipitation inhibitors during the dissolution of carbamazepine-nicotinamide (CBZ-NCT) cocr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-019-2622-7
更新日期:2019-04-23 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000045226.42859.b8
更新日期:2004-10-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-019-2663-y
更新日期:2019-08-02 00:00:00
abstract:PURPOSE:Recently identified organic solute transporter (Ost) alpha and beta are located on the basolateral membrane of enterocytes and may be responsible for the intestinal absorption of many substrates including bile acids. In the present study, the mechanism governing the transcriptional regulation of their expressio...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9163-6
更新日期:2007-02-01 00:00:00
abstract::Moexipril [2-[(1-ethoxycarbonyl)-3-phenylpropyl]amino-1-oxopropyl]-6, 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (S,S,S)], an ester prodrug of an ACE inhibitor, was formulated in controlled-release preparations with a range of in vitro release rates, to provide a prolonged input of drug in vivo. Howe...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015919413103
更新日期:1989-09-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9805-y
更新日期:2009-04-01 00:00:00
abstract:PURPOSE:Melanoma is an aggressive neoplasm with a propensity for metastases and resistance to therapy. Previously, we showed that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present in green tea, resulted in a significant decrease in the viability and growth of melanoma and induction of ap...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-010-0054-5
更新日期:2010-06-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018910114436
更新日期:1994-01-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000026444.67883.83
更新日期:2004-05-01 00:00:00
abstract:PURPOSE AND METHODS:Data from 358 pharmacist-patient encounters in 12 community pharmacies were used to investigate the association of prescription status, patient age, patient gender, and patient question asking with the content of pharmacist-patient communication. RESULTS:There was an association between prescriptio...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012084207399
更新日期:1997-02-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1025053115583
更新日期:2003-08-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-1861-0
更新日期:2016-05-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0944-9
更新日期:2013-04-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018912100826
更新日期:1993-08-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012164520429
更新日期:1997-10-01 00:00:00
abstract::The pentahydrate (alpha form) of cefazolin sodium (CEZ) exhibited sharp X-ray diffraction peaks, while the dehydrated alpha form showed weak but distinct diffraction peaks. As expected the amorphous form exhibited a diffuse and halo diffraction pattern. The X-ray procedure to estimate the degree of crystallinity of CE...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015984300692
更新日期:1988-07-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016209020160
更新日期:1995-06-01 00:00:00