Dexamethasone Concentration in Vitreous and Serum After Oral Administration

Weijtens, Olga; Schoemaker, Rik C.; Cohen, Adam F.; Romijn, Fred P.H.T.M.; Lentjes, Eef G.W.M.; Rooij, Jeroen van; Meurs, Jan C. van

doi:10.1016/s0002-9394(98)00003-8

Cited by 79 publications

(62 citation statements)

References 11 publications

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“…administration of equivalent amounts of drug (Tsuji et al, 1988). Similar results have been found with peribulbar injection compared with systemic oral administration of prednisone (Weijtens et al, 1997(Weijtens et al, , 1998. Using the iontophoresis device the CCI signi®cantly increased concentrations of MP in all ocular tissues and¯uids of the rabbit eye compared to the i.v.…”

Section: Discussionsupporting

confidence: 59%

“…Frequent topical administration of eye drops or subconjunctival injections may induce suf®cient concentrations of drugs within the anterior segment of the eye (Mc Catney et al, 1965;Benson, 1974;Demailly, Hamard and Luton, 1976;Leibowitz and Kupferman, 1977). However, to achieve effective tissue concentrations in the posterior segment of the eye, systemic administration, intravitreal or periocular injections are necessary (Barry, Rousseau and Babineau, 1969;Demailly et al, 1976;Bodker et al, 1993;Weijtens et al, 1997Weijtens et al, , 1998. Lachaud (1965) ®rst used iontophoresis of corticosteroids for the treatment of ocular in¯ammation in patients.…”

Section: Introductionmentioning

confidence: 99%

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Transscleral Coulomb-controlled Iontophoresis of Methylprednisolone into the Rabbit Eye: Influence of Duration of Treatment, Current Intensity and Drug Concentration on Ocular Tissue and Fluid Levels

Behar‐Cohen

Aouni

Gautier

et al. 2002

Experimental Eye Research

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Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Transscleral Coulomb-controlled Iontophoresis of Methylprednisolone into the Rabbit Eye: Influence of Duration of Treatment, Current Intensity and Drug Concentration on Ocular Tissue and Fluid Levels

Behar‐Cohen

Aouni

Gautier

et al. 2002

Experimental Eye Research

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“…Anti-IL-8 activity of high-dose ibuprofen was compared to that of dexamethasone, a corticosteroid, which has a well-established record of IL-8 down-regulation in respiratory epithelium [25]. Both drugs were used at clinically relevant concentrations: ibuprofen at 100 mg/l (480 µ M ) [4,5] and dexamethasone at 1.7 µg/l (5 n M ) [26,27]. …”

Section: Introductionmentioning

confidence: 99%

Ibuprofen Modulates NF-ĸB Activity but Not IL-8 Production in Cystic Fibrosis Respiratory Epithelial Cells

et al. 2009

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Background: High-dose ibuprofen is clinically effective in cystic fibrosis (CF); however, its molecular mechanisms are poorly understood. Objective: To test the hypothesis that clinically relevant concentrations of ibuprofen suppress activation of nuclear factor (NF)-ĸB and thus down-regulate stimulated interleukin (IL)-8 production in CF respiratory epithelial cells. Methods: The majority of experiments were conducted in CFTE29o– cells (F508del-mutated CF transmembrane regulator, CFTR). Key experiments were confirmed in CFBE41o– cells (F508del-mutated CFTR) and 1HAEo– cells (wild-type CFTR). NF-ĸB and IL-8 were stimulated with tumour necrosis factor (TNF)-α or IL-1β. NF-ĸB and IL-8 suppression by ibuprofen (480 µM) was compared to dexamethasone (5 nM). Results: Both TNF-α and IL-1β activated NF-ĸB and stimulated IL-8 production. Both ibuprofen and dexamethasone demonstrated comparably modest suppression of NF-ĸB transcriptional activity. However, ibuprofen had no effect on stimulated IL-8 mRNA and protein. By contrast, dexamethasone significantly down-regulated stimulated IL-8 mRNA and protein. Conclusions: The present data do not support the hypothesis that ibuprofen down-regulates IL-8 production in response to TNF-α and IL-1β in CF respiratory epithelium. Suppression of NF-ĸB transcriptional activity does not discriminate between anti-inflammatory drugs with or without effects on IL-8 production. We speculate that NF-ĸB-independent mechanisms may be responsible for anti-IL-8 effects of dexamethasone.

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“…Previous studies of DEX conducted in vitro have used concentrations between 100 nM and 1 mM (22,28,42,43). The concentrations of DEX (250 nM) and PRED (1 mM) used in these experiments are physiologically relevant concentrations, calculated on the basis of recommended dosing relative to blood volume, and for DEX correspond to levels measured in the serum after oral administration (44,45). It is therefore tempting to speculate that these results identify a novel effect of GCs that could contribute to therapeutic efficacy in treating intestinal inflammation, by inhibiting CCR9-medated adhesion and migration of effector T cells.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoids Suppress CCR9-Mediated Chemotaxis, Calcium Flux, and Adhesion to MAdCAM-1 in Human T Cells

Wendt

White

Ferry

et al. 2016

The Journal of Immunology

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CCR9 expressed on T lymphocytes mediates migration to the small intestine in response to a gradient of CCL25. CCL25-stimulated activation of α4β7 integrin promotes cell adherence to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed by vascular endothelial cells of the intestine, further mediating gut-specific homing. Inflammatory bowel disease is a chronic inflammatory condition that primarily affects the gastrointestinal tract and is characterized by leukocyte infiltration. Glucocorticoids (GCs) are widely used to treat inflammatory bowel disease but their effect on intestinal leukocyte homing is not well understood. We investigated the effect of GCs on the gut-specific chemokine receptor pair, CCR9 and CCL25. Using human peripheral blood-derived T lymphocytes enriched for CCR9 by cell sorting or culturing with all-trans retinoic acid, we measured chemotaxis, intracellular calcium flux, and α4β7-mediated cell adhesion to plate-bound MAdCAM-1. Dexamethasone (DEX), a specific GC receptor agonist, significantly reduced CCR9-mediated chemotaxis and adhesion to MAdCAM-1 without affecting CCR9 surface expression. In contrast, in the same cells, DEX increased CXCR4 surface expression and CXCL12-mediated signaling and downstream functions. The effects of DEX on human primary T cells were reversed by the GC receptor antagonist mifepristone. These results demonstrate that GCs suppress CCR9-mediated chemotaxis, intracellular calcium flux, and α4β7-mediated cell adhesion in vitro, and these effects could contribute to the efficacy of GCs in treating intestinal inflammation in vivo.

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Dexamethasone Concentration in Vitreous and Serum After Oral Administration

Cited by 79 publications

References 11 publications

Transscleral Coulomb-controlled Iontophoresis of Methylprednisolone into the Rabbit Eye: Influence of Duration of Treatment, Current Intensity and Drug Concentration on Ocular Tissue and Fluid Levels

Transscleral Coulomb-controlled Iontophoresis of Methylprednisolone into the Rabbit Eye: Influence of Duration of Treatment, Current Intensity and Drug Concentration on Ocular Tissue and Fluid Levels

Ibuprofen Modulates NF-ĸB Activity but Not IL-8 Production in Cystic Fibrosis Respiratory Epithelial Cells

Glucocorticoids Suppress CCR9-Mediated Chemotaxis, Calcium Flux, and Adhesion to MAdCAM-1 in Human T Cells

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