Abstract：
:Transport studies using intestinal brush-border membrane vesicles isolated from rats and rabbits have failed to demonstrate proton- or Na(+)-dependent carrier-mediated transport of thyrotropin-releasing hormone (TRH), despite a pharmacologically relevant oral bioavailability. To examine the hypothesis that reported levels of oral bioavailability reflect predominantly a paracellular rather than transcellular route for transepithelial transport of TRH, we have studied TRH transport in cultured epithelial cell types of intestinal (Caco-2 and T84) and renal (MDCK I, MDCK II, and LLC-PK1) origin, whose paracellular pathways span the range of permeability values observed in natural epithelia. Transport of TRH across monolayers of intestinal Caco-2 cells was similar to the flux of mannitol (approximately 1-4% per 4 hr), and unlike other putative substrates for the di-/tripeptide carrier, apical-to-basolateral transport was not increased by the presence of an acidic pH in the apical chamber. TRH transport did not show saturation, being uneffected in the presence of 20 mM cold TRH. In each cell type studied TRH and mannitol transport were similar and positively correlated with the conductance of the cell layers, consistent with a passive mechanism of absorption. This evidence suggests that, providing that a peptide is resistant to luminal hydrolysis, small but pharmacologically significant amounts of peptide absorption may be achieved by passive absorption across a paracellular route.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Thwaites DT,Hirst BH,Simmons NLdoi
10.1023/a:1018947430018subject
Has Abstractpub_date
1993-05-01 00:00:00pages
674-81issue
5eissn
0724-8741issn
1573-904Xjournal_volume
10pub_type
杂志文章abstract：:The absorption of insulin across the vaginal mucosa into the systemic circulation was studied in ovariectomized rats given subsequent estrogen treatment. Blood glucose levels were determined as an indirect measure of insulin absorption, and the effect of various enhancers on the hypoglycemic response was investigated....
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015892630637
更新日期：1992-07-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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journal_title：Pharmaceutical research
pub_type： 社论
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更新日期：2007-12-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1014451203619
更新日期：2002-03-01 00:00:00
abstract：:Unsymmetrical aryl(heteroaryl)methyl isopropyl ester analogues of nifedipine, in which the 2-nitrophenyl group at C-4 is replaced by a 2- or 3-pyridyl substituent, were synthesized and evaluated as calcium-channel antagonists using guinea pig ileal longitudinal smooth muscle. The point of attachment of the C-4 pyridyl...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015941706008
更新日期：1990-09-01 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：: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
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016340106299
更新日期：1985-07-01 00:00:00
abstract：:Using brine shrimp lethality to direct fractionation, extracts of the bark of Annona bullata Rich. (Annonaceae) have yielded 16 alpha-hydroxy-(-)-kauranoic acid as a bioactive plant constituent. This previously known diterpene showed significant (ED50 8.25 x 10(-2) micrograms/ml) and selective cytotoxicity against A-5...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015819422479
更新日期：1990-04-01 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：:The pharmacokinetics of methylergometrine were investigated in the rat, with emphasis on the role of biliary excretion and enterohepatic recirculation in the overall disposition of the drug. A linked-rat model, where the bile from a rat receiving a constant rate of iv infusion of methylergometrine was allowed to flow ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015871122537
更新日期：1990-01-01 00:00:00
abstract：PURPOSE:To determine whether a Protected Graft Copolymer (PGC) containing fatty acid can be used as a stabilizing excipient for GLP-1 and whether PGC/GLP-1 given once a week can be an effective treatment for diabetes. METHODS:To create a PGC excipient, polylysine was grafted with methoxypolyethyleneglycol and fatty ac...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0542-2
更新日期：2012-01-01 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：:Under the heading "Methods-Synthesis of the Bioreducible Modified-PAE (mPAE)", on page 3, line 14-17, there is an error. The quantity unit of PAE and 2-iminothiolane hydrochloride needs to be corrected to mg instead of g. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章,已发布勘误
doi：10.1007/s11095-018-2488-0
更新日期：2018-09-05 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0784-7
更新日期：2012-09-01 00:00:00
abstract：PURPOSE:We investigated the characteristics of transport of an organic anion, p-aminohippurate (PAH), at the apical membrane in a kidney epithelial cell line OK. METHODS:Efflux and uptake of [14C]PAH across the apical membrane were measured using OK cell monolayers grown on microporous membrane filters. RESULTS:PAH e...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1021437306990
更新日期：2002-12-01 00:00:00
abstract：PURPOSE:Novel itraconazole (ITZ)-based dry powders for inhalation (DPI) were optimized for aerodynamic and dissolution properties and contained excipients that are acceptable for inhalation. METHODS:The DPI were produced by spray drying solutions. The drug content, crystallinity state, and morphological evaluation of ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0779-4
更新日期：2012-10-01 00:00:00
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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
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-2011-4
更新日期：2016-12-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1086-4
更新日期：2013-10-01 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:To employ in vitro experiments combined with computational fluid dynamics (CFD) analysis to determine which aerodynamic factors were most responsible for deaggregating carrier-free powders to form micrometer and submicrometer aerosols from a capsule-based platform. METHODS:Eight airflow passages were evaluated...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1001-z
更新日期：2013-06-01 00:00:00
abstract：:The bioavailability of a new sustained-release potassium chloride (KCl) tablet, designed for once-a-day dosing, was compared to a KCl elixir using urinary excretion data. The study utilized 25 male volunteers dosed in a crossover design in a dietary/activity-controlled environment. The regimens consisted of a total of...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016438413297
更新日期：1987-10-01 00:00:00
abstract：PURPOSE:Doxorubicin was chemically conjugated to a terminal end group of poly(D,L-lactic-co-glycolic acid) [PLGA] and the doxorubicin-PLGA conjugate was formulated into nanoparticles to sustain the release of doxorubicin. METHODS:A hydroxyl terminal group of PLGA was activated by p-nitrophenyl chloroformate and reacte...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018908421434
更新日期：1999-07-01 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：PURPOSE:The aim was to evaluate fluorescent molecular rotors (DCVJ and CCVJ), which are mainly sensitive to viscosity, for the characterization of polysorbate-containing IgG formulations and compare them to the polarity-sensitive dyes ANS, Bis-ANS and Nile Red. METHODS:IgG formulations with polysorbate 20 or 80 were s...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-0020-2
更新日期：2010-02-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016061330387
更新日期：1996-06-01 00:00:00
abstract：:The transport of thyrotropin releasing hormone (TRH) in rabbit buccal mucosa in vitro has been investigated with respect to (a) rate and type of metabolism of TRH on mucosal and serosal sides of buccal mucosa, (b) mechanism of TRH transport including charge effect on its permeability, and (c) pathway and rate-limiting...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015883217858
更新日期：1992-09-01 00:00:00
abstract：PURPOSE:Study the radiolysis of solid-state metoclopramide hydrochloride at various absorbed doses. Elucidate the structure of the degradation products to gain information on the radiolysis mechanisms. METHODS:Solid-state metoclopramide samples were irradiated at several doses with gamma rays and high-energy electrons...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-0019-x
更新日期：2006-06-01 00:00:00
