Abstract：
PURPOSE:Grapefruit juice (GJ) is known to increase the oral bioavailability of many CYP3A-substrates by inhibiting intestinal phase-I metabolism. However, the magnitude of AUC increase is often insignificant and highly variable. Since we earlier suggested that CYP3A and P-glycoprotein (P-gp) form a concerted barrier to drug absorption, we investigated the role of P-gp in GJ-drug interactions. METHODS:The transcellular bidirectional flux of drugs that are (i) CYP3A-and/or P-gp substrates (Vinblastine, Cyclosporine, Digoxin, Fexofenadine, Losartan) or that are (ii) primary CYP3A-substrates (Felodipine, Nifedipine) was evaluated across MDCK-MDR1 cell monolayers with or without GJ, verifying monolayer integrity at all times. RESULTS:While both apical-to-basal (A-B) and basal-to-apical (B-A) fluxes of all CYP3A/P-gp substrates tested were increased in the presence of GJ, the resulting net efflux (B-A/A-B) was in all cases significantly greater with GJ than control (Vin, 28.0 vs. 5.1; CsA, 9.9 vs. 2.8; Dig, 22. 9 vs. 14.7, Fex, 22.3 vs. 11.1, Los, 39.6 vs. 26). In contrast, no such GJ flux effect was observed with Fel and Nif, substrates of CYP3A only (2 vs. 1.7 and 1.2 vs. 1.3). CONCLUSIONS:GJ significantly activates P-gp-mediated efflux of drugs that are substrates of P-gp, potentially partially counteracting the CYP3A-inhibitory effects of GJ.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Soldner A,Christians U,Susanto M,Wacher VJ,Silverman JA,Benet LZdoi
10.1023/a:1011902625609subject
Has Abstractpub_date
1999-04-01 00:00:00pages
478-85issue
4eissn
0724-8741issn
1573-904Xjournal_volume
16pub_type
杂志文章abstract：PURPOSE:The objective of this study was to investigate the possible influence of probenecid on morphine transport across the blood-brain barrier (BBB) in rats. METHODS:Microdialysis probes, calibrated using retrodialysis by drug, were placed into the striatum and jugular vein of seven Sprague-Dawley rats. Morphine was...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1023250900462
更新日期：2003-04-01 00:00:00
abstract：PURPOSE:Adenoviruses are being developed for diseases of the gastrointestinal tract. Several in vitro assays were used to predict stability of PEGylated adenovirus along the GI tract and determine in vivo gene transfer after oral administration. METHODS:Recombinant adenovirus was modified with monomethoxypoly(ethylene...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1025714412337
更新日期：2003-09-01 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1007/s11095-015-1693-3
更新日期：2015-10-01 00:00:00
abstract：:Despite substantial research carried out over the last decades, it remains difficult to understand the wide range of pharmacological effects of dopaminergic agents. The dopaminergic system is involved in several neurological disorders, such as Parkinson's disease and schizophrenia. This complex system features multipl...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
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更新日期：2018-02-15 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0410-0
更新日期：2011-07-01 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. ...
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pub_type： 杂志文章,已发布勘误
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更新日期：2018-09-05 00:00:00
abstract：:Penetration of various compounds through shed snake skin was measured in vitro to examine the effect of lipophilicity and molecular size of a compound on permeability through this model membrane. The permeabilities were found to be controlled by the lipophilicity and the molecular size of the permeant. The smaller and...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015902308676
更新日期：1990-12-01 00:00:00
abstract：:The effect of freezing on formation of soluble and insoluble aggregates of human growth hormone (hGH) was studied. The amount of soluble aggregates was affected very little by freezing regardless of the cooling rate. In contrast, the formation of insoluble aggregates (particulates), as determined by light scattering i...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015888704365
更新日期：1991-11-01 00:00:00
abstract：:The role of a bile salt (sodium taurocholate) and lipolysis products (monoglyceride and fatty acid) in the intestinal absorption of a poorly water-soluble drug, diazepam, was investigated. Absorption rates and bioavailabilities were determined with the in situ rat gut technique of Doluisio et al. and analyzing the dia...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016312827680
更新日期：1985-09-01 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1023/a:1014809916407
更新日期：1999-08-01 00:00:00
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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
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更新日期：1999-04-01 00:00:00
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更新日期：2004-05-01 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1023/a:1012114825513
更新日期：1997-06-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9680-6
更新日期：2008-11-01 00:00:00
abstract：:Five aliphatic 5'-esters of 5-iodo-2'deoxyuridine (IDU) were synthesized via an acid chloride alcoholysis reaction. The solubility in pH 7.4 phosphate buffer, lipophilicity as determined by partition experiments in octanol/pH 7.4 buffer, and cytotoxicity of these potential prodrugs were evaluated. The esters showed a ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015968113838
更新日期：1988-11-01 00:00:00
abstract：PURPOSE:This study was carried out to examine the blood-brain barrier (BBB) transport of human basic fibroblast growth factor (bFGF) and investigate its mechanism. METHODS:The BBB transport of 125I-bFGF was measured by several in vivo methods including intravenous administration, in situ internal carotid artery perfus...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007570509232
更新日期：2000-01-01 00:00:00
abstract：:Enoximone and piroximone are cardiotonic agents for use in patients with congestive heart failure. Electroanalytical studies revealed that the dihydroimidazolone functionality was oxidizable and that this property can be analytically useful. The compounds undergo a two-electron, irreversible oxidation in neutral to ac...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015811830830
更新日期：1991-07-01 00:00:00
abstract：PURPOSE:With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity. METHODS:Mono- and multi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020354809581
更新日期：2002-09-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：
更新日期：1999-11-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：1995-06-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章
doi：10.1023/a:1016002322692
更新日期：1996-04-01 00:00:00
abstract：:Physicochemical effects caused by intestinal fluids on drugs in the gastrointestinal (GI) tract can be a contributing factor in food induced changes in bioavailability. To identify physicochemical properties of gemfibrozil that may be altered by endogenous and dietary lipids, in vitro studies were conducted in model s...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018967401000
更新日期：1994-12-01 00:00:00
abstract：PURPOSE:To investigate the effect of tyrphostin 8 (T-8), a GTPase inhibitor, on transferrin receptor (TfR)-mediated transcytosis of insulin-transferrin (In-Tf) conjugate in cultured enterocyte-like Caco-2 cells and on gastrointestinal (GI) absorption of In-Tf in streptozotocin (STZ)-induced diabetic rats. METHODS:Caco...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011032502097
更新日期：2001-02-01 00:00:00
abstract：PURPOSE:The purpose of this study was to determine the existence of insulin-degrading enzyme (EC 3.4.22.11) (IDE) in rat intestinal enterocytes. METHODS:Subcellular fractionation, biochemical characterization, immunoprecipitation, and western blots were employed. RESULTS:Insulin-degrading activity was localized in th...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016263926946
更新日期：1995-08-01 00:00:00
abstract：PURPOSE:The aim of this work was to evaluate whether improved topical delivery of finasteride, focussed to the hair follicles of human scalp skin could be achieved with application of short durations of heat and use of specific chemical penetration enhancers. METHODS:Franz cell experiments with human scalp skin were p...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02822-y
更新日期：2020-05-31 00:00:00
abstract：PURPOSE:Nasal delivery is a favorable route for vaccination against most respiratory infections, as antigen deposited in the nasal turbinate and Waldeyer's ring areas induce mucosal and systemic immune responses. However, little is known about the nasal distribution of the vaccines, specifically for infants. METHODS:A...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02976-9
更新日期：2021-01-15 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007500412442
更新日期：2000-05-01 00:00:00
abstract：:Intraocular enzymes convert the ketoxime analogues of some beta-adrenergic blockers via a sequential bioactivation process involving hydrolysis to the corresponding ketones followed by reduction to the aryloxyaminoalcohols, which then exert known and predictable physiological and pharmacological effects only at the si...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015863521513
更新日期：1990-07-01 00:00:00
abstract：PURPOSE:Drug particle physical properties are critical for the efficiency of a drug delivered to the lung. The purpose of this study was to produce ultrafine sumatriptan succinate particles for inhalation. METHODS:Sumatriptan succinate particles were produced via reactive precipitation without any surfactants. Several...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9586-3
更新日期：2008-09-01 00:00:00
