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 permeability (a surrogate marker of toxicity) after administration of 20 mg and 40 mg/kg regular release (powder) and modified release formulations [sustained release (SR) beads and diethyl-beta-cyclodextrin (DCD):TA inclusion complex (INC)]. Urinary excretion of oral doses of GI permeability probes sucrose and 51Cr-EDTA was determined as measures of gastroduodenal and distal intestine, respectively. Pharmacokinetics of TA enantiomers were also studied following administration of a single 20 mg/kg dose of racemic TA as oral SR beads and iv solution. For powder and INC, previously reported pharmacokinetic data were used. RESULTS:Regular powder significantly increased the permeability at the gastroduodenal level. Modified-release formulations, on the other hand, did not cause damage in the gastroduodenum but produced significant increase in the permeability of the lower intestine. Consequently, to assess the pharmacokinetic-pharmacodynamic relationship, a new model was developed in which contribution of toxicity resulted from direct exposure to the drug was considered. CONCLUSIONS:Since the observed site of GI damage corresponds to the site of release and absorption of NSAID from the formulation, the possibility of a shift in the site of damage must be considered for the modified release formulations. A parallel evaluation of upper and lower GI toxicity is essential for a complete assessment of NSAID-induced GI damage.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Vakily M,Khorasheh F,Jamali Fdoi
10.1023/a:1018887216098subject
Has Abstractpub_date
1999-01-01 00:00:00pages
123-9issue
1eissn
0724-8741issn
1573-904Xjournal_volume
16pub_type
杂志文章abstract:PURPOSE:To elucidate the catalytic mechanism of the esterase-like activity of serum albumin (SA), the reactivity of SA from six species was investigated using p-nitrophenyl esters as model substrates. METHODS:The effect of pH and the energetic and thermodynamic profiles of SA were determined for all species for p-nitr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000016241.84630.06
更新日期:2004-02-01 00:00:00
abstract:PURPOSE:The aim of this study was to develop a labile sphingosine-based liposome for intramuscular gene delivery. METHODS:Sphingosine-based liposomes were formulated in a range of solutions with phosphatidylcholine, then were associated to DNA. The physico-chemical characteristics of the sphingosine/EPC liposomes and ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1019894008885
更新日期:2002-08-01 00:00:00
abstract:PURPOSE:Changes in drug absorption and first-pass metabolism have been reported throughout the pediatric age range. Our aim is to characterize both intestinal and hepatic CYP3A-mediated metabolism of midazolam in children in order to predict first-pass and systemic metabolism of CYP3A substrates. METHODS:Pharmacokinet...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2458-6
更新日期:2018-07-30 00:00:00
abstract:PURPOSE:The purpose of this study was to evaluate glucose responsiveness in HepG2 human hepatoma cells transduced by a recombinant adeno-associated virus (rAAV) vector containing the insulin gene promoter. and to investigate the effect of protamine sulfate on rAAV-mediated gene delivery. METHODS:Recombinant AAV vector...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1010923924844
更新日期:2001-07-01 00:00:00
abstract:PURPOSE:Indocyanine green (ICG), an FDA-approved near infrared (NIR) dye, has potential application as a contrast agent for tumor detection. Because ICG binds strongly to plasma proteins and exhibits aqueous, photo, and thermal instability, its current applications are largely limited to monitoring blood flow. To addre...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-010-0190-y
更新日期:2010-09-01 00:00:00
abstract::A method to provide near-constant sustained release of high molecular weight, water-soluble proteins from polyanhydride microspheres is described. The polyanhydrides used were poly(fatty acid dimer) (PFAD), poly(sebacic acid) (PSA), and their copolymers [P(FAD-SA)]. P(FAD-SA) microspheres containing proteins of differ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018929531410
更新日期:1993-04-01 00:00:00
abstract::Various diesters of 9-[(1,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) were screened in order to identify a derivative with improved oral absorption. The solubilities and dissolution rates decreased with increasing chain length and branching of the ester group. However, the dipropionate ester showed an anomalously fas...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016462801968
更新日期:1987-04-01 00:00:00
abstract::The intrasubject and intersubject variabilities for CGS 16617, an angiotensin converting enzyme inhibitor, were evaluated in an open-label, repeat single-dose bioavailability trial. Eight healthy male volunteers each received a 20-mg oral dose of CGS 16617 as an aqueous solution on four separate occasions. Components ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015954609527
更新日期:1989-04-01 00:00:00
abstract::Growing tumors develop additional new blood vessels to meet the demand for adequate nutrients and oxygen, a process called angiogenesis. Cancer is a highly complex disease promoted by excess angiogenesis; interfering with this process poses for an attractive approach for controlling tumor growth. This hypothesis led t...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-008-9634-z
更新日期:2008-12-01 00:00:00
abstract:PURPOSE:The effect of the molecular weight of dextran on the molecular mobility and protein stability of freeze-dried serum gamma-globulin (BGG) formulations was studied. The stabilizing effect of higher molecular weight dextran is discussed in relation to the molecular mobility of the formulations. METHODS:The molecu...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012194220970
更新日期:1997-06-01 00:00:00
abstract::The crystal growth kinetics of theophylline monohydrate from aqueous buffered supersaturated solutions were investigated at 10, 20, 30, and 40 degrees C. Crystallization experiments were carried out isothermally at pH 6. During growth the crystal count and size distributions were monitored in situ. The growth rate was...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015817109932
更新日期:1991-05-01 00:00:00
abstract:PURPOSE:This paper aims to investigate the immunoinhibitory properties of a lymph nodes-targeting suppressive oligonucleotide (ODN) for the potential treatment of autoimmune diseases or chronic inflammation. METHODS:Synthetic suppressive ODN engineered with an albumin-binding diacyl lipid at the 5'-terminal (lipo-ODN)...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2344-2
更新日期:2018-02-08 00:00:00
abstract:OBJECTIVES:We recently demonstrated that fibrin-based tissue engineered blood vessels (TEV) exhibited vascular reactivity, matrix remodeling and sufficient strength for implantation into the veins of an ovine animal model, where they remained patent for 15 weeks. Here we present an approach to improve the mechanical pr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9499-6
更新日期:2008-05-01 00:00:00
abstract:PURPOSE:To determine the different conformations of the acyloxyalkoxy-linked cyclic prodrug 1 of the model hexapeptide 2 in solution and to investigate the relationship between these solution conformations and the cellular permeability characteristics of this prodrug. METHODS:Two-dimensional Homonuclear Hartmann-Hahn ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016484522113
更新日期:1996-11-01 00:00:00
abstract:PURPOSE:To measure the diffusion of nanometer polymersomes through tissue engineered human oral mucosa. METHODS:In vitro models of full thickness tissue engineered oral mucosa (TEOM) were used to assess the penetration properties of two chemically different polymersomes comprising two of block copolymers, PMPC-PDPA an...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-009-9882-6
更新日期:2009-07-01 00:00:00
abstract:PURPOSE:We prepared injectable microspheres for controlled release of TAK-029, a water-soluble GPIIb/IIIa antagonist and discussed the characteristics of controlled release from microspheres. METHODS:Copoly(dl-lactic/glycolic)acid (PLGA) microspheres were used for controlled release of TAK-029 [4-(4-amidinobenzoylglyc...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012190304074
更新日期:1997-09-01 00:00:00
abstract::HPLC analyses of GM-CSF in solution mixtures containing both GM-CSF and HSA showed losses of GM-CSF which could not be accounted for using conventional electrophoretic and/or RP-HPLC techniques. Further investigation of these mixtures by immunoblotting and by immunoaffinity chromatography demonstrated the presence of ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018900701657
更新日期:1994-03-01 00:00:00
abstract:PURPOSE:This study demonstrates the nasal administration (NA) of nanoemulsions complexed with the plasmid encoding for IDUA protein (pIDUA) as an attempt to reach the brain aiming at MPS I gene therapy. METHODS:Formulations composed of DOPE, DOTAP, MCT (NE), and DSPE-PEG (NE-PEG) were prepared by high-pressure homogen...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2503-5
更新日期:2018-09-26 00:00:00
abstract:PURPOSE:Penetration enhancers (PEs) enhancing efficacy depends on two processes: PEs release from patches and action on skin. Compared with their action on skin, PEs release process was poorly understood. Therefore, the purpose of this study was to make a mechanistic understanding of PEs release from acrylic pressure-s...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02901-0
更新日期:2020-08-13 00:00:00
abstract:PURPOSE:To study the biorelevant drug release from novel starch-based polyvinyl alcohol capsules (S-PVA-C). The effect of the shell material is studied by considering microstructural formulation changes during hydration. METHODS:Two different self-emulsifying systems containing either fenofibrate or probucol were fill...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1152-y
更新日期:2014-01-01 00:00:00
abstract:PURPOSE:Tissue partitioning is an important component of drug distribution and half-life. Protein binding and lipid partitioning together determine drug distribution. METHODS:Two structure-based models to predict partitioning into microsomal membranes are presented. An orientation-based model was developed using a mem...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-2085-z
更新日期:2017-03-01 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:The purpose of this study was to assess the effect of several chemical permeation enhancers on the buccal permeability of nicotine and to image the spatial distribution of nicotine in buccal mucosa with and without buccal permeation enhancers. METHODS:The impact of sodium taurodeoxycholate (STDC), sodium dodec...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2332-y
更新日期:2018-02-21 00:00:00
abstract:PURPOSE:A rapid immune response is required to prevent death from Anthrax, caused by Bacillus anthracis. METHOD:We formulated a vaccine carrier comprised of acetalated dextran microparticles encapsulating recombinant protective antigen (rPA) and resiquimod (a toll-like receptor 7/8 agonist). RESULTS:We were able to p...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-0975-x
更新日期:2013-05-01 00:00:00
abstract:PURPOSE:To develop novel biomineral-binding liposomes (BBL) for the prevention of orthopedic implant associated osteomyelitis. METHODS:A biomineral-binding lipid, alendronate-tri(ethyleneglycol)-cholesterol conjugate (ALN-TEG-Chol), was synthesized through Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (a versatile...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0812-7
更新日期:2012-11-01 00:00:00
abstract::An empirical mass-transfer model for enteric-coating dissolution that uses in vivo dissolution data to characterize the pH-dependent solubility properties of the polymer film and a mass-transfer coefficient determined from in vivo dissolution or disintegration studies is developed. Once the in vivo mass-transfer coeff...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018986827350
更新日期:1993-02-01 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
abstract::The transepithelial transport of arginine vasopressin (AVP) across cultured rat alveolar epithelial cell monolayers was studied. At 0.1 nM donor [125I]AVP, the radiolabel flux measured in the apical-to-basolateral (AB) direction was about 10 times greater than that in the reverse (BA) direction. HPLC analyses of the b...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018918022865
更新日期:1994-11-01 00:00:00
abstract::One of the authors has his name incorrectly indexed in PubMed and SpringerLink as "Laird Forrest M" (last name "Laird Forrest"). His name should index as "Forrest M. Laird" with last name as "Forrest". ...
journal_title:Pharmaceutical research
pub_type: 杂志文章,已发布勘误
doi:10.1007/s11095-018-2463-9
更新日期:2018-07-25 00:00:00
abstract::A series of carboxyfluorescein (CF)-containing multilamellar vesicle (MLV) dispersions was prepared and extruded through polycarbonate membranes ranging in size from 0.2 to 5 microns. Vesicle dispersions were nebulized for 80 min using a Collison nebulizer, and the release of CF was monitored during nebulization. Solu...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015896121377
更新日期:1991-02-01 00:00:00