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. However, pharmacokinetic studies with the controlled-release dosage forms in humans produced plasma profiles with the same characteristics and time to peak as an immediate-release capsule. In vitro dissolution data from the controlled-release dosage form, as well as the known characteristics of the polymer used to control drug release from the dosage form, suggest no reason to suspect an abrupt halt to the in vivo release of the drug after 1-2 hr. The lack of sustained blood levels is, therefore, most likely due to failure of the GI tract to absorb the drug beyond some location in the upper small intestine, i.e., site-specific absorption. This theory is supported by a series of computer simulations involving moexipril and the active moiety, moexipril diacid. Possible mechanisms include poor drug permeability, a pH effect whereby the zwitterionic form of the drug is more rapidly absorbed, and esterase cleavage of moexipril to the poorly absorbed moexipril diacid.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Grass GM,Morehead WTdoi
10.1023/a:1015919413103subject
Has Abstractpub_date
1989-09-01 00:00:00pages
759-65issue
9eissn
0724-8741issn
1573-904Xjournal_volume
6pub_type
杂志文章abstract：:Cyclosporine (CsA) is commercially available for oral administration as a solution in olive oil with alcohol and an emulsifier. To improve its variable absorption and low patient acceptability, several oral formulations were prepared and tested in vitro and in vivo in dogs. A tablet formulation prepared by direct comp...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015815614959
更新日期：1991-04-01 00:00:00
abstract：:Alpha- and beta-cyclodextrins and their hydroxypropyl derivatives were converted by the reaction with chlorosulfonic acid in pyridine to the corresponding sulfates. Cyclodextrin sulfates were shown by fast-atom bombardment mass spectrometry (negative ion mode, triethanolamine matrix) to be mixtures with nearly symmetr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015854402122
更新日期：1991-09-01 00:00:00
abstract：PURPOSE:To develop a new technique, spray freeze drying, for preparing protein aerosol powders. Also, to compare the spray freeze-dried powders with spray-dried powders in terms of physical properties and aerosol performance. METHODS:Protein powders were characterized using particle size analysis, thermogravimetric an...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018828425184
更新日期：1999-02-01 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：PURPOSE:The amphiphilic block copolymer Pluronic P85 (P85) increases the permeability of the blood-brain barrier (BBB) with respect to a broad spectrum of drugs by inhibiting the drug efflux transporter, P-glycoprotein (Pgp). In this regard, P85 serves as a promising component for CNS drug delivery systems. To assess t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000048189.79606.6e
更新日期：2004-11-01 00:00:00
abstract：OBJECTIVE:The objective of this work was to determine plasma protein adsorption and macrophage phagocytosis of biodegradable polyanhydride, polylactic acid and polylactic-co-glycolic acid microspheres prepared by both spray-drying and solvent evaporation techniques. METHODS:Microspheres were characterized by scanning ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011935222652
更新日期：1998-02-01 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：PURPOSE:We evaluated the effect of luminal bacterial metabolism on intestinal absorption of azetirelin in rats. In vitro characteristics of bacterial metabolism of azetirelin were also investigated with the goal of overcoming the low stability of the peptidic drug against luminal microorganisms. METHODS:Plasma azetire...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012141025938
更新日期：1997-08-01 00:00:00
abstract：:The transport characteristics of the renin inhibitor ((3S,4S)-4-[N-morpholinoacetyl-(1-naphthyl)-L-alanyl-N-methyl-(4-t hiazolyl)-L- alanyl]amino-3-hydroxy-5-cyclohexyl-1-(4-pyridyl)-1-pentanone; CH3-18) in rat small intestinal brush-border membrane vesicles (BBMV) were examined by a rapid filtration technique. The up...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018900124257
更新日期：1994-10-01 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
abstract：PURPOSE:To study the relative thermodynamic and kinetic stabilities of neotame anhydrate polymorphs A, D, F, and G, and to develop a quantitative method for analyzing polymorphic mixtures of A and G by powder X-ray diffractometry (PXRD). METHODS:Based on the melting points, heats of fusion, and densities of the four p...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020334305038
更新日期：2002-09-01 00:00:00
abstract：PURPOSE:To compare the ability of alkyl-aryl isothiocyanates (ITCs) to increase the activities of the Phase 2 detoxification enzymes NAD[P]H:quinone acceptor oxidoreductase 1 (NQO1) and glutathione S-transferases (GST) in rat tissues in vivo and in cells in vitro. MATERIALS AND METHODS:Twelve alkyl-aryl ITCs and the f...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9595-2
更新日期：2008-09-01 00:00:00
abstract：:Determination of methadone (MET) in biological fluids can serve to adjust dosages in patients suffering from cancer pain or participating in methadone maintenance programs. We developed a gas chromatographic assay using nitrogen-phosphorus detection. The method involves a single-step extraction from alkalized plasma, ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018904825958
更新日期：1993-03-01 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:To study Cereport (RMP-7, bradykinin B2 agonist) effects on human brain microvascular endothelial cell (HBMEC) monolayer permeability. METHODS:HBMEC grown on transwell membranes were exposed to Cereport. The monolayer permeability was determined with [14C]-inulin (MW. 5,200) and [3H]-dextran (MW. 70,000). RES...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018938722768
更新日期：1999-09-01 00:00:00
abstract：PURPOSE:To develop a semi-mechanistic population pharmacokinetic model based on gastric emptying function for acetaminophen plasma concentration in critically ill patients tolerant and intolerant to enteral nutrition before and after prokinetic therapy. METHODS:Acetaminophen plasma concentrations were available from a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0290-8
更新日期：2011-02-01 00:00:00
abstract：PURPOSE:The purpose of this study was to characterize the amorphous state of ursodeoxycholic acid (UDCA) samples by using isothermal microcalorimetry, X-ray diffraction, infrared (IR) spectroscopy and solid state carbon 13 nuclear magnetic resonance (13C-NMR) spectroscopy, and to demonstrate the application of the ther...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012114825513
更新日期：1997-06-01 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：:RNA interference (RNAi) strategies include double-stranded RNA (dsRNA), small interfering RNA (siRNA), short hairpin RNA (shRNA), and microRNA (miRNA). As this is a highly specific technique, efforts have been made to utilize RNAi towards potential knock down of disease-causing genes in a targeted fashion. RNAi has th...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-011-0608-1
更新日期：2011-12-01 00:00:00
abstract：:Losartan, an antihypertensive agent in clinical development, was found to exist in two enantiotropic polymorphic forms, a low-temperature stable form (Form I) and a high-temperature stable form (Form II), the temperatures at which they are stable being related to the transition temperature. X-ray powder diffraction pa...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018973530443
更新日期：1993-06-01 00:00:00
abstract：PURPOSE:This study aimed to investigate the impact of the size of X-ray iodinated contrast agent in nano-emulsions, on their toxicity and fate in vivo. METHODS:A new compound, triiodobenzoate cholecalciferol, was synthetized, formulated as nano-emulsions, and followed after i.v. administration in mice by X-ray imaging...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1813-0
更新日期：2016-03-01 00:00:00
abstract：:5'-Ester derivatives of 5-iodo-2'-deoxyuridine (IDU) with varying degrees of lipophilicity were examined to evaluate the effectiveness of lipophilic ester prodrugs for enhanced and sustained delivery of IDU to the brain parenchyma. Approximately 1.0% (1.0 +/- 0.19; n = 4) of the total radioactivity was found in the br...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015803922401
更新日期：1992-09-01 00:00:00
abstract：PURPOSE:To assess the efficacy of lipid-protein-sugar particles (LPSPs) in providing prolonged duration local anesthesia by percutaneous injection. METHODS:Bupivacaine-containing LPSPs were characterized and optimized in vitro. Male Sprague-Dawley rats were given sciatic nerve blocks with bupivacaine-containing LPSPs....
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1026470831256
更新日期：2000-10-01 00:00:00
abstract：PURPOSE:This study was conducted to investigate the cause of incomplete protein release from photopolymerized poly(ethylene glycol) (PEG) hydrogels and verify the protein-protection mechanism provided by iminodiacetic acid (IDA). METHODS:The in vitro release of bovine serum albumin (BSA) from PEG hydrogels prepared un...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-9395-x
更新日期：2006-03-01 00:00:00
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 quantifi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-9019-x
更新日期：2005-01-01 00:00:00
abstract：PURPOSE:Chemically modified heparin-DOCA was prepared and found to have markedly lower anticoagulant activity than heparin. In the present study, we elucidated the antiangiogenic and antitumoral activities of heparin-DOCA derivative. METHODS:To evaluate the antiangiogenic and antitumoral effects of heparin-DOCA, capil...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9139-6
更新日期：2007-01-01 00:00:00
abstract：PURPOSE:To assess the uridine diphosphate (UDP)-glucuronosyltransferase (UGT) isozymes involved in the glucuronidation of niflumic acid in human liver. METHODS:The glucuronidation activity of niflumic acid was determined in liver microsomes and recombinant UGT isozymes by incubation of niflumic acid with UDP-glucuroni...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-0250-5
更新日期：2006-07-01 00:00:00
abstract：PURPOSE:Effects of polyvinylpyrrolidone (PVP) molecular weight on the solid-state intermolecular interactions among probucol/PVP/sodium dodecyl sulfate (SDS) ternary ground mixtures (GM) and the formation of nanoparticles were investigated by solid-state NMR spectroscopy. MATERIALS AND METHODS:Ternary GMs of probucol ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9089-z
更新日期：2006-11-01 00:00:00
abstract：PURPOSE:This study aimed to characterize the transepithelial transport of miltefosine (HePC), the first orally effective drug against visceral leishmaniasis, across the intestinal barrier to further understand its oral absorption mechanism. MATERIALS AND METHODS:Caco-2 cell monolayers were used as an in vitro model of...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9170-7
更新日期：2007-03-01 00:00:00
abstract：PURPOSE:A theory and computer programs running on Microsoft Excel for Windows for calculation of solution pH, buffer formula, and buffer capacity at a given ionic strength and temperature were developed. The theory does not limit the category of buffer components, the number of buffer components, or the number of ioniz...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012037819211
更新日期：1997-03-01 00:00:00
