Abstract：
PURPOSE:To evaluate the impact of intestinal first-pass metabolism (Fg) by cytochrome P4503A (CYP3A) and uridine 5'-diphosphate-glucuronosyltransferases (UGT) on in vivo oral absorption of their substrate drugs. METHODS:CYP3A and UGT substrates were orally administered to portal-vein cannulated (PV) rats to evaluate their intestinal availability (Fa · Fg). In the case of CYP3A substrates, vehicle or 1-aminobenzotriazole (ABT), a potent inhibitor of CYP enzymes, was pretreated to assess Fg separately from Fa (Enzyme-inhibition method). On the other hand, since potent inhibitors of UGT have not been identified, Fg of UGT substrate was calculated from total amount of metabolites generated in enterocytes (Metabolite-distribution method). RESULTS:After oral administration of CYP3A substrates in ABT-pretreated rats, the portal and systemic plasma concentrations of the metabolite were nearly the same, indicating almost complete inhibition of intestinal CYP3A-mediated metabolism. Using Enzyme-inhibition method, Fg of midazolam (1 mg/kg) was calculated as 0.71. Additionally, total amount of raloxifene-6-glucuronide generated in enterocytes after oral administration of raloxifene was estimated using Metabolite-distribution method and Fg of raloxifene (0.98 μmol/kg) was calculated as 0.21. CONCLUSIONS:PV rats enabled in vivo quantitative assessment of intestinal first-pass metabolism by CYP3A and UGT. This method is useful for clarifying the cause of low bioavailability.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Matsuda Y,Konno Y,Hashimoto T,Nagai M,Taguchi T,Satsukawa M,Yamashita Sdoi
10.1007/s11095-014-1489-xsubject
Has Abstractpub_date
2015-02-01 00:00:00pages
604-16issue
2eissn
0724-8741issn
1573-904Xjournal_volume
32pub_type
杂志文章abstract：PURPOSE:To study the degradation of oxaliplatin in chloride media and evaluate the cytotoxicity of oxaliplatin in normal and chloride-deficient medium. METHODS:The products of the reaction of oxaliplatin with chloride were separated on a Hypercarb S column with a mobile phase containing 40% methanol in 0.05 M ammonia ...
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:In this work a novel pH-responsive nanoscale polymer network was investigated for potential applications in nanomedicine. These consisted of a polybasic core surface stabilized with poly(ethylene glycol) grafts. The ability to control swelling properties via changes in core hydrophobicity and crosslinking feed ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9704-2
更新日期：2009-01-01 00:00:00
abstract：PURPOSE:Chitosan-based polymeric micelles (CBPMs) are considered as promising carriers for delivery of anticancer drugs, imaging agents and genes. To optimize the physicochemical, pharmaceutical and biological properties of CBPMs, the molecular mechanisms behind the self-assembly behavior of chitosan (CHI) amphiphilic ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1750-y
更新日期：2015-12-01 00:00:00
abstract：PURPOSE:VLPs displaying tumor targeting single-chain variable fragments (VLP-rscFvs) which targets tumor-associated glycoprotein-72 (TAG-72) marker protein have a potential for immunotherapy against colon carcinoma tumors. In this study, scFvs anchored on VLPs using glycosylphosphatidylinositol (GPI) were prepared to t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1316-4
更新日期：2014-08-01 00:00:00
abstract：PURPOSE:The purpose of this study is to investigate the characteristics of pGlu-L-Dopa-Pro as a prodrug of L-Dopa. METHODS:pGlu-L-Dopa-Pro and L-Dopa-Pro were synthesized using the standard procedures of peptide synthesis. The conversion of pGlu-L-Dopa-Pro to L-Dopa was studied using pyroglutamyl aminopeptidase I and ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016239321494
更新日期：1995-07-01 00:00:00
abstract：PURPOSE:The purpose of this study was to evaluate an effect of the proteolytic enzyme papain on permeation of low molecular weight heparin (LMWH) in vitro and in vivo. MATERIALS AND METHODS:In vitro permeation studies were performed using rat small intestine as permeation barrier. In order to determine the ratio of pa...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9226-8
更新日期：2007-05-01 00:00:00
abstract：PURPOSE:We have already demonstrated that the HMG-CoA reductase inhibitor, pravastatin is actively taken up by isolated rat hepatocytes via a multispecific anion transporter (Yamazaki et al., Am. J. Physiol. 264, G36-44, (1993)). We further attempted the quantitative evaluation of this uptake in different experimental ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016226024587
更新日期：1995-11-01 00:00:00
abstract：PURPOSE:The aim of the study is to investigate the effect of polymer blending on entrapment and release of ganciclovir (GCV) from poly(D,L-lactide-co-glycolide) (PLGA) microspheres using a set of empirical equations. METHODS:Two grades of PLGA, PLGA 7525 [D,L-lactide:glycolide(75:25), MW 90,000-126,000 Da] and Resomer...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-9042-6
更新日期：2006-01-01 00:00:00
abstract：:The immune system has the ability to recognize and kill pre-cancer and cancer cells. However, with the immune system's surveillance, the survival tumor cells learn how to escape the immune system after immunoselection. Cancer immunotherapy develops strategies to overcome these problems. Nanomedicine applications in ca...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
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更新日期：2011-02-01 00:00:00
abstract：:A series of multilamellar liposome dispersions was prepared from lipids of soy phosphatidylcholine or hydrogenated soy phosphatidylcholine containing from 0 to 30 mol% of either cholesterol, stearylamine, or dipalmitoyl phosphatidylglycerol. The liposome dispersions were aerosolized with a Collison nebulizer for 80 mi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015924124180
更新日期：1990-11-01 00:00:00
abstract：:A sensitive activity assay for high volume evaluation of human renin inhibitory peptides (RIPs) in rat sera (range 2-80 ng/ml) was developed based on the low affinity of RIPs to rat renin and their high affinity to human renin. The utility of this activity assay was tested by measuring concentrations of a human RIP, U...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015883709275
更新日期：1990-04-01 00:00:00
abstract：PURPOSE:Although flomoxef (FMOX) has attracted substantial attention as an antibiotic against extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-producing E. coli), the pharmacokinetics/pharmacodynamics (PK/PD) characteristics of FMOX against ESBL-producing E. coli is unclear. The aim of this study was t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02977-8
更新日期：2021-01-06 00:00:00
abstract：PURPOSE:To investigate the effect of surface functionalization of mesoporous silica nanoparticles (MSN) on crystallization, loading, release and activity of mitoxantrone (MTX). METHODS:Thiol-, amine-, and mixed thiol/amine-functionalized MSN were synthesized and characterized by electron microscopy, thermogravimetry, ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0766-9
更新日期：2012-09-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016309923717
更新日期：1986-06-01 00:00:00
abstract：:The binding of diflunisal to hydroxypropyl-beta-cyclodextrin (HP beta CD), bovine serum albumin (BSA), human serum albumin (HSA), normal human plasma, and mixed solutions of HP beta CD/protein was studied at 25 degrees C, pH 7.4, by potentiometry using an electrode selective to diflunisal. The experimental data for di...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018901912619
更新日期：1994-01-01 00:00:00
abstract：PURPOSE:Nonlinear conjugation metabolic rate of valproic acid (VPA) has been speculated previously from plasma elimination and liver concentration of VPA in guinea pigs. The purposes of the present study were to assess our speculation by direct measurement of VPA glucuronidation rate in vitro. METHODS:VPA at various c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016028707130
更新日期：1996-08-01 00:00:00
abstract：PURPOSE:In this study, we developed and evaluated a novel method to produce insulin-loaded hydrophilic microspheres allowing high encapsulation efficiency and the preservation of peptide stability during particle processing. The preparation method used the diffusion of water by an excess of solvent starting from a wate...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000036919.94865.57
更新日期：2004-08-01 00:00:00
abstract：PURPOSE:An integrated ionic mobility-pore model for epidermal iontophoresis is developed from theoretical considerations using both the free volume and pore restriction forms of the model for a range of solute radii (rj) approaching the pore radii (rp) as well as approximation of the pore restriction form for rj/rp < 0...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011907201096
更新日期：1998-10-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2622-7
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016397520991
更新日期：1986-04-01 00:00:00
abstract：PURPOSE:Heparin immobilized porous poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared for sustained release of basic fibroblast growth factor (bFGF) to induce angiogenesis. MATERIALS AND METHODS:Porous PLGA microspheres having primary amine groups on the surface were prepared using an oil-in-water (O/...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9039-9
更新日期：2006-08-01 00:00:00
abstract：PURPOSE:The objective of this study was to evaluate nanoparticle uptake by the Caco-2 monolayer model in vitro. Special emphasis was placed on the localization and the quantification of the uptake of fluorescently labeled polystyrene and poly(lactic-co-glycolic acid) (PLGA) nanoparticles. METHODS:Intracellular fluores...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015393710253
更新日期：2002-05-01 00:00:00
abstract：PURPOSE:Novel therapeutics are greatly needed that target specific pathological receptors and pathways involved in Neuropathic Pain (NP). Extending our previous work published in this Journal on Group I metabotropic glutamate receptor (mGluR) modulators, we now investigate the therapeutic potential of niclosamide in mo...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-2027-9
更新日期：2016-12-01 00:00:00
abstract：:The effects of skin storage, skin preparation, skin pretreatment with a penetration enhancer, and skin barrier removal by adhesive tape-stripping on the concurrent cutaneous transport and metabolism of nitroglycerin (GTN) have been studied in vitro using hairless mouse skin. Storing the skin for 10 days at 4 degrees C...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015822431178
更新日期：1992-03-01 00:00:00
abstract：PURPOSE:To study the physical and release properties of different molecular weight (MW) pH- and temperature-responsive statistical terpolymers and beads of N-isopropylacrylamide (NIPAAm), butylmethacrylate (BMA) and acrylic acid (AA). METHODS:Random terpolymers of varying MW were synthesized with NIPAAm/BMA/AA of feed...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018813700535
更新日期：1999-06-01 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:Platinum-based therapies are the first line treatments for most types of cancer including ovarian cancer. However, their use is associated with dose-limiting toxicities and resistance. We report initial translational studies of a theranostic nanoemulsion loaded with a cisplatin derivative, myrisplatin and pro-a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1660-z
更新日期：2015-08-01 00:00:00
abstract：PURPOSE:Supramolecular Biovectors (SMBV) consist of cross-linked cationic nanoparticles surrounded by a lipid membrane. The purpose was to study the structure of the lipid membrane and to characterise its interaction with the nanoparticles in order to differentiate SMBV from other polymer/lipid associations. METHODS:T...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007504124603
更新日期：2000-07-01 00:00:00
abstract：PURPOSE:The aim of this study is to extend our previous studies to investigate the TerplexDNA synthetic gene carrier system in pharmacokinetics, biodistribution, and gene expression in major organs after systemic administration. METHODS:The stability of the TerplexDNA system was analyzed in vitro with a serum incubati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013081710135
更新日期：2001-09-01 00:00:00
abstract：PURPOSE:The lack of an in vivo diagnostic test for AD has prompted the targeting of amyloid plaques with diagnostic imaging probes. We describe the development of a contrast agent (CA) for magnetic resonance microimaging that utilizes the F(ab')2 fragment of a monoclonal antibody raised against fibrillar human Abeta42 ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9600-9
更新日期：2008-08-01 00:00:00
