Abstract：
:The origin of the microheterogeneity of a highly purified antiinflammatory humanized monoclonal antibody prepared in mammalian cell culture has been investigated. This antibody is an IgG directed toward human CD18 (a subunit of leukocyte integrins). When the IgG preparation is subjected to isoelectric focusing, it is found to contain four major species with pI values ranging from 6 to 7. Although the relative amounts of each form differ and some species are present only in small quantities, each has been isolated by a combination of high-resolution anion-exchange chromatography and isoelectric focusing. Comparative studies reveal no detectable differences in overall secondary (far UV circular dichroism) or tertiary (intrinsic fluorescence) structure, molecular weight (laser-desorption mass spectroscopy), or antigen binding activity. When each of the isolated species is incubated under conditions which favor deamidation, it is converted to forms of lower pI which appear to correspond to naturally observed species. While the isolated light chain is relatively homogeneous, the heavy chain exhibits a pattern of isoelectric focusing bands similar to that of the intact immunoglobulin. These results suggest that in this case, charge microheterogeneity is due to the sequential deamidation of the immunoglobulin heavy chain.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Tsai PK,Bruner MW,Irwin JI,Ip CC,Oliver CN,Nelson RW,Volkin DB,Middaugh CRdoi
10.1023/a:1018912417607subject
Has Abstractpub_date
1993-11-01 00:00:00pages
1580-6issue
11eissn
0724-8741issn
1573-904Xjournal_volume
10pub_type
杂志文章abstract：PURPOSE:To develop an efficient tumor vasculature-targeted polymeric micelle delivery system for combretastatin A4 (CA4), a novel antivascular agent. METHODS:CA4-loaded micelles were prepared from poly (ethylene glycol)-b-poly (d, l-lactide) copolymers. RGD peptides that target integrins alphavbeta3 and alphavbeta5, m...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0184-9
更新日期：2010-09-01 00:00:00
abstract：:The pharmacokinetics of Sb was examined in 29 patients with cutaneous leishmaniasis following the intramuscular administration of a dose of sodium stibogluconate equivalent to 600 mg of Sb. Blood was sampled at different time intervals from each patient and Sb was measured in whole blood by electrothermal atomic absor...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016251023427
更新日期：1995-01-01 00:00:00
abstract：PURPOSE:This study was conducted to investigate in vivo the impact of interferon-alpha (IFN)-alpha on P-glycoprotein (P-gp) activity in rats by studying how its administration modifies the bioavailability of digoxin, a fairly pure P-gp substrate. METHODS:Human recombinant IFN-alpha was given to rats (n = 5-7 per group...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-7415-5
更新日期：2005-11-01 00:00:00
abstract：PURPOSE:Cisplatin, is recognized as a first line therapeutic for the treatment of non-small cell lung cancer (NSCLC). Cisplatin resistance is identified as the most detrimental complication during treatment and has been associated with upregulation of several genes, such as the anti-apoptotic gene survivin. In this stu...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-2016-z
更新日期：2016-12-01 00:00:00
abstract：PURPOSE:Modulation of 5-HT3 receptor in the central nervous system (CNS) is a promising approach for treatment of neuropathic pain. The goal was to evaluate the role of P-glycoprotein (Pgp) in limiting exposure of different parts of the CNS to ondansetron (5-HT3 receptor antagonist) using wild-type and genetic knockout...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02929-2
更新日期：2020-09-28 00:00:00
abstract：PURPOSE:To evaluate the influence of the main biopharmaceutical factors on the viability of a new probiotic yeast strain, using dynamic in vitro systems simulating human gastric/small intestinal (TIM) and large intestinal (ARCOL) environments. METHODS:The viability of Saccharomyces cerevisiae CNCM I-3856 throughout th...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0620-5
更新日期：2012-06-01 00:00:00
abstract：PURPOSE:This study aims to develop a characterization method for coating structure based on image analysis, which is particularly promising for the rational design of coated particles in the pharmaceutical industry. METHODS:The method applies the MATLAB image processing toolbox to images of coated particles taken with...
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:An ex vivo intact toe model was developed to assess two different applicator designs for iontophoretic delivery of terbinafine into the nail only or the nail and surrounding skin. METHODS:Iontophoretic permeation studies were carried out on intact cadaver toes using nail-only and nail/skin applicators with a c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9934-y
更新日期：2009-09-01 00:00:00
abstract：PURPOSE:For selective inhibition of endothelial cell activation in chronic inflammation, we have developed a dexamethasone-anti-E-selectin immunoconjugate. The present study was performed to evaluate the cellular handling of this immunoconjugate by activated primary endothelial cells and to compare its drug delivery ca...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020769716288
更新日期：2002-11-01 00:00:00
abstract：:A number of substituted phthalimide, 1, 8-naphthalimide, succinimide and glutarimide derivatives demonstrated significant hypolipidemic activity at 20 mg/kg/ day, I.P. after 16 days dosing. The N-(n-pentyl) succinimide proved to be the most potent analogue of the new compounds, lowering serum triglyceride levels 51 % ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016346018962
更新日期：1984-11-01 00:00:00
abstract：PURPOSE:The purpose of this study was (a) to suggest a novel dermatopharmacokinetic (DPK) approach from which pharmacokinetic parameters relevant to the bioequivalence (BE) assessment of a topical formulation can be deduced while circumventing the need for numerous measurements and assumptions, and (b) to investigate w...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2724-2
更新日期：2020-01-02 00:00:00
abstract：PURPOSE:Using monolayers of human pancreatic adenocarcinoma cells (Panc-1) that express multidrug resistance-associated protein (MRP), the present work investigates the effects of Pluronic block copolymers on the functional activity of MRP. METHODS:The studies examined the accumulation and efflux of the MRP selective ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018873702411
更新日期：1999-03-01 00:00:00
abstract：PURPOSE:Proteasome inhibition induces endoplasmic reticulum (ER) stress and compensatory autophagy to relieve ER stress. Disturbance of intracellular calcium homeostasis can lead to ER stress and alter the autophagy process. It has been suggested that inhibition of the proteasome disrupts intracellular calcium homeosta...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1139-8
更新日期：2013-09-01 00:00:00
abstract：PURPOSE:One of the drawbacks of polycationic and cationic liposomal gene transfer is its sensitivity to serum. Gene therapy requires the transfectant-DNA complex to be resistant to serum as well as blood. Since Ca2+ has proved to be an efficient cofactor of polycationic gene transfer, we decided to investigate its effe...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007581700996
更新日期：2000-02-01 00:00:00
abstract：PURPOSE:The objective of this study was to determine the pharmacokinetics and safety for NX1838 following injection into the vitreous humor of rhesus monkeys. METHODS:Plasma and vitreous humor pharmacokinetics were determined following a single bilateral 0.25, 0.50, 1.0, 1.5, or 2.0 mg/eye dose. In addition, the pharm...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007657109012
更新日期：2000-12-01 00:00:00
abstract：:The present review discusses drugs and counter ions suitable for ion pair transport (IPT). Ion pairing is shown to effectively increase the lipophilicity and transport rate of polar drugs across lipid membranes. The proposed mechanisms of IPT are discussed in detail. A marked change in drug properties upon ion pair fo...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1015963128124
更新日期：1989-09-01 00:00:00
abstract：PURPOSE:To evaluate the potential for the acidic intestinal unstirred water layer (UWL) to induce drug supersaturation and enhance drug absorption from intestinal mixed micelles, via the promotion of fatty acid absorption. METHODS:Using a single-pass rat jejunal perfusion model, the absorptive-flux of cinnarizine and ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1104-6
更新日期：2013-12-01 00:00:00
abstract：UNLABELLED:PURPOSE; The aim of this study was to investigate asparagine (Asn) deamidation and aspartate (Asp) isomerization and to measure the content of isoaspartate (isoAsp) in recombinant human interleukin-11 (rhIL-11). METHODS:The rhIL-11 control and heat stressed samples were characterized with trypsin and endopr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1019814713428
更新日期：2002-08-01 00:00:00
abstract：PURPOSE:Evista (raloxifene HCl) is a nonsteroidal selective estrogen receptor modulator that displays estrogen agonist effects on bone and lipid metabolism but estrogen antagonist effects on the breast and endometrium. The potential for drug-drug interaction between raloxifene and warfarin was assessed in 15 healthy po...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1010904815275
更新日期：2001-07-01 00:00:00
abstract：PURPOSE:HSP90 (Heat shock protein 90kD) has been validated as a therapeutic target in Castrate Resistant Prostate Cancer. Unfortunately, HSP90 inhibitors suffer from dose-limiting toxicities that hinder their clinical applications. Previously developed polymeric delivery systems for HSP90 inhibitors had either low drug...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2249-5
更新日期：2017-12-01 00:00:00
abstract：PURPOSE:The clinical utility of anthracyclines like idarubicin (IDA) is limited by the occurrence of multidrug resistance and cardiotoxicity. Previous studies have demonstrated that the multidrug transporter P-glycoprotein (P-gp) is present in the heart and have suggested that it exerts a protective function. We sought...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013022212738
更新日期：2001-11-01 00:00:00
abstract：PURPOSE:To better understand the nature of drug-excipient interactions we have studied the phase behavior of amorphous binary and ternary mixtures of citric acid, indomethacin and PVP, as model systems. METHODS:We have prepared amorphous mixtures by co-melting or coprecipitation from solvents, and have measured glass ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011983606606
更新日期：1998-08-01 00:00:00
abstract：PURPOSE:The pharmacokinetics of corticosteroids in pregnancy were analyzed to assess maternal/fetal disposition and factors controlling fetal exposure. Area/Moment equations and compartmental models for estimating pharmacokinetic parameters from single dose data during pregnancy were developed. METHODS:Betamethasone i...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-7681-7
更新日期：2004-12-01 00:00:00
abstract：PURPOSE:The purpose of this study was to develop a new computational fluid dynamics (CFD)-based model of the complex transport and droplet drying kinetics within a laboratory-scale spray dryer, and relate CFD-predicted drying parameters to powder aerosolization metrics from a reference dry powder inhaler (DPI). METHOD...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02806-y
更新日期：2020-05-21 00:00:00
abstract：PURPOSE:Three types of acyl tetragastrin (TG), acetyl-TG (C2-TG), butyryl-TG (C4-TG) and caproyl-TG (C6-TG) were synthesized and their in vitro intestinal permeability characteristics were examined using Caco-2 monolayers. METHODS:The disappearance of acyl-TGs from the apical side of Caco-2 monolayers was estimated by...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011997404306
更新日期：1998-09-01 00:00:00
abstract：PURPOSE:The purpose of this study was (i) to develop glancing angle x-ray powder diffractometry (XRD) as a method for profiling phase transformations as a function of tablet depth; and (ii) to apply this technique to (a) study indomethacin crystallization during dissolution of partially amorphous indomethacin tablets a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000012163.89163.f8
更新日期：2004-01-01 00:00:00
abstract：:The technique of Affinity capillary electrophoresis (ACE) is a useful tool to characterize complexation and partition equilibria. A wide range of applications in pharmaceutics has been presented: the determination of pKA values, of association constants between drugs and cyclodextrins or amphiphilic compounds as well ...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：
更新日期：1999-11-01 00:00:00
abstract：PURPOSE:Fractal kinetics was used for the analysis of the carrier-mediated transport for drugs across the intestinal epithelial cells. METHODS:The transport was examined under various agitation rates using a monolayer of Caco-2 cells and rabbit ileum sheets. RESULTS:The passive transport of antipyrine across Caco-2 c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011994230346
更新日期：1998-04-01 00:00:00
abstract：:A biopharmaceutics drug classification scheme for correlating in vitro drug product dissolution and in vivo bioavailability is proposed based on recognizing that drug dissolution and gastrointestinal permeability are the fundamental parameters controlling rate and extent of drug absorption. This analysis uses a transp...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016212804288
更新日期：1995-03-01 00:00:00
abstract：:New generation vaccines, particularly those based on recombinant proteins and DNA, are likely to be less reactogenic than traditional vaccines but are also less immunogenic. Therefore, there is an urgent need for the development of new and improved vaccine adjuvants. Adjuvants can be broadly separated into two classes...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1016104910582
更新日期：2002-06-01 00:00:00
