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Developmental Pharmacology and... 1993The single-dose pharmacokinetics of dexamethasone were studied in 7 extremely low birth weight infants of mean (+/- SD) gestational age 25.6 +/- 0.5 weeks suffering... (Clinical Trial)
Clinical Trial
The single-dose pharmacokinetics of dexamethasone were studied in 7 extremely low birth weight infants of mean (+/- SD) gestational age 25.6 +/- 0.5 weeks suffering bronchopulmonary dysplasia. A mean peak dexamethasone concentration of 250.5 +/- 70.7 ng/ml was obtained following an intravenous bolus dose (0.369 +/- 0.04 mg/kg dexamethasone) of dexamethasone sodium phosphate. Dexamethasone was measured in plasma by HPLC. Mean clearance (0.143 +/- 0.028 litres/kg/h) was approximately half that reported previously in children and adults, while the half-life (9.26 +/- 3.34 h) was 2- to 3-fold longer than in these patients. The volume of distribution (1.9 +/- 0.483 litres/kg) was larger than reported in a previous study in adults, but was similar to that determined in pediatric and adult patients in another study.
Topics: Bronchopulmonary Dysplasia; Chromatography, High Pressure Liquid; Dexamethasone; Female; Half-Life; Humans; Infant, Low Birth Weight; Infant, Newborn; Injections, Intravenous; Male
PubMed: 7828455
DOI: 10.1159/000457564 -
Rheumatology International 1994Thirty-five patients with diffuse systemic sclerosis were studied in a randomized, placebo-controlled, double-blind study. Seventeen patients received intravenous... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Thirty-five patients with diffuse systemic sclerosis were studied in a randomized, placebo-controlled, double-blind study. Seventeen patients received intravenous dexamethasone "pulse" therapy, while 18 patients received placebo. Each "pulse" consisted of 100 mg dexamethasone in 250 ml 5% dextrose infused intravenously over 1 h. Pulse therapy was repeated every month for 6 months. Assessment of disease status with various parameters was done at entry and at completion of trial, i.e. after 6 months. Significant improvement in skin involvement was seen in the study group, with the total skin score (TSS) decreasing from 28.5 +/- 12.2 to 25.8 +/- 12.8, while in the control group, TSS increased from 30.6 +/- 13.2 to 34.7 +/- 10. Similarly, significant improvement was noted in the flexion index. Other parametres that included extension index, maximum oral opening, range of movement of joints, functional disability score, Raynaud's phenomenon (frequency and duration), ESR, proteinuria, chest X-ray, ECG, lung function tests, barium swallow and antinuclear antibody were unchanged. Adverse effects of therapy were limited to an increased incidence of minor chest infections. It is concluded that intravenous pulse dexamethasone may be useful in the treatment of diffuse systemic sclerosis.
Topics: Adult; Dexamethasone; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Scleroderma, Systemic; Treatment Outcome
PubMed: 7839076
DOI: 10.1007/BF00300808 -
Analytical Chemistry Jun 2015Selective probing of dexamethasone in excised human skin using soft X-ray spectromicroscopy provides quantitative concentration profiles as well as two-dimensional drug...
Selective probing of dexamethasone in excised human skin using soft X-ray spectromicroscopy provides quantitative concentration profiles as well as two-dimensional drug distribution maps. Element- and site-selective excitation of dexamethasone at the oxygen K-edge with the lateral step width adjusted to 1 μm provides detailed information on the location of the drug in the different skin layers. The key of this work is to probe dexamethasone selectively at the carbonyl site (C3) by the O 1s → π* transition, providing also a most efficient way to quantify the drug concentration as a function of penetration depth in correlation with structural properties of the skin containing carboxyl and amide oxygen sites occurring at higher transition energy than dexamethasone. Following drug exposure for 4 h, the glucocorticoide is located in about equal amounts in the stratum corneum, the outermost horny layer of skin, and in the viable epidermis, whereas in the dermis no dexamethasone is detected. In the stratum corneum, most of the lipophilic drug is found in regions between corneocytes, where epidermal lipids are dominating.
Topics: Dexamethasone; Healthy Volunteers; Humans; Molecular Conformation; Skin; Spectrum Analysis; X-Rays
PubMed: 25942614
DOI: 10.1021/acs.analchem.5b00800 -
Journal of Medicinal Chemistry Jun 1991The C-21 methanesulfonate ester of the synthetic glucocorticoid dexamethasone (Dex) is an efficient electrophilic affinity label of glucocorticoid receptors and exhibits...
The C-21 methanesulfonate ester of the synthetic glucocorticoid dexamethasone (Dex) is an efficient electrophilic affinity label of glucocorticoid receptors and exhibits irreversible antiglucocorticoid activity. In an effort to obtain other affinity labeling steroids with differing biological activities, several new derivatives of Dex were prepared which contained a reactive electrophilic substituent at various distances from the C-21 position. All compounds displayed relatively low affinity for rat glucocorticoid receptors (less than or equal to 8% of that of Dex) in a cell-free competition assay. Nevertheless, one compound, dexamethasone 21-(beta-isothiocyanatoethyl) thioether (Dex-NCS), appeared to be an affinity label by virtue of its ability to block the cell-free exchange binding of [3H]Dex. [3H]Dex-NCS was thus synthesized and reacted with cell-free receptors to give, after analysis on denaturing SDS-polyacrylamide gels, only one specifically labeled species at 98 kDa, which is the molecular weight of authentic rat glucocorticoid receptor. These data directly establish Dex-NCS as a new affinity label for glucocorticoid receptors. Data on the reactivity of Dex-NCS and the stability of [3H]Dex-NCS-labeled receptors suggest that a cysteine SH group has been labeled.
Topics: Affinity Labels; Binding Sites; Cyanates; Dexamethasone; Electrophoresis, Polyacrylamide Gel; Isothiocyanates; Receptors, Glucocorticoid; Steroids
PubMed: 2061919
DOI: 10.1021/jm00110a002 -
Journal of the Medical Association of... Nov 2015Laparoscopic cholecystectomy is one of the most common procedures in surgery. Post-operative pain and post- operative nausea and vomiting (PON) are frequently events... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Laparoscopic cholecystectomy is one of the most common procedures in surgery. Post-operative pain and post- operative nausea and vomiting (PON) are frequently events after laparoscopic cholecystectomy and cause distress to patients. Dexamethasones are known for analgesic, anti-inflammatory, immune-modulating and anti-emetic effects. Therefore, preoperative dexamethasone administration may reduce postoperative pain and postoperative nausea vomiting after laparoscopic cholecystectomy.
OBJECTIVE
This study aims to determine the effects of single-dose preoperative intravenous dexamethasone on clinical outcome such as postoperative pain nausea and vomiting in patients undergoing laparoscopic cholecystectomy.
MATERIAL AND METHOD
This is a prospective randomized controlled trial study. Eighty patients undergoing elective laparoscopic cholecystectomy were randomized to dexamethasone group and control group. Dexamethasone group received 8 mg (2 ml) of intravenous dexamethasone 60-90 minute before surgery whereas control group received 2 ml of normal saline 60-90 minute before surgery. Patients received a similar standardized anesthesia, surgical and multimodal analgesic treatment. The pain score, nausea and vomiting at 1, 6, 24 hours after surgery and before discharge including analgesic consumption and antiemetic required was recorded in both groups. Preoperative and postoperative erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured.
RESULTS
No significant difference existed between two groups regarding age, sex, previous operation, operation time and hospital stays. All of the patients had no postoperative complication. Postoperative pain score, nausea and vomiting at 1st and 6th hours in dexamethasone group were significantly reduced in comparison with control group. Analgesic consumption, antiemetic requirement and CRIP postoperative were significantly decreased in dexamethasone group.
CONCLUSION
Single-dose preoperative dexamethasone 8 mg 60-90 minute before induction of anesthesia improved clinical outcome in terms of significantly less nausea, vomiting, pain at first 6 hours and less inflammatory response after laparoscopic cholecystectomy compared to placebo. The preoperative dexamethasone should be used as routine in patients undergoing laparoscopic cholecystectomy.
Topics: Administration, Intravenous; Adult; Aged; Anti-Inflammatory Agents; Antiemetics; Cholecystectomy, Laparoscopic; Dexamethasone; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Pain, Postoperative; Postoperative Nausea and Vomiting; Preoperative Care; Prospective Studies; Thailand
PubMed: 27276842
DOI: No ID Found -
Tissue Barriers 2019Glucocorticoid hormones affect gene expression via activation of glucocorticoid receptor NR3C1, causing modulation of inflammation and autoimmune activation. The...
Glucocorticoid hormones affect gene expression via activation of glucocorticoid receptor NR3C1, causing modulation of inflammation and autoimmune activation. The glucocorticoid Dexamethasone is an important pharmaceutical for the treatment of colitis and other inflammatory bowel diseases. While suppressive effects of glucocorticoids on activated immune cells is significant, their effects upon epithelial cells are less well studied. Previous research shows that the effects of Dexamethasone treatment on polarized Caco-2 cell layer permeability is delayed for >10 treatment days (as measured by transepithelial electrical resistance). intestinal epithelial cells turn over every 3-5 days; we therefore hypothesized that culture age may produce marked effects on gene expression, potentially acting as a confounding variable. To investigate this issue, we cultured polarized Caco-2 monolayers during a 30-day timecourse with ~15 days of continuous Dexamethasone exposure. We collected samples during the timecourse and tested differential expression using a 250-plex gene expression panel and Nanostring nCounter® system. Our custom panel was selectively enriched for KEGG annotations for tight-junction, actin cytoskeleton regulation, and colorectal cancer-associated genes, allowing for focused gene ontology-based pathway enrichment analyses. To test for confounding effects of time and Dexamethasone variables, we used the Nanostring nSolver differential expression data model which includes a mixturenegative binomial modelwith optimization. We identified a time-associated "EMT-like" signature with differential expression seen in important actomyosin cytoskeleton, tight junction, integrin, and cell cycle pathway genes. Dexamethasone treatment resulted in a subtle yet significant counter-signal showing suppression of actomyosin genes and differential expression of various growth factor receptors.
Topics: Caco-2 Cells; Cytoskeleton; Dexamethasone; Gene Expression; Humans; Time Factors
PubMed: 31438773
DOI: 10.1080/21688370.2019.1651597 -
European Journal of Clinical... 1987We have given single high doses of dexamethasone phosphate by intravenous infusion as an antiemetic to 15 cancer patients receiving regimens containing cisplatin and/or...
We have given single high doses of dexamethasone phosphate by intravenous infusion as an antiemetic to 15 cancer patients receiving regimens containing cisplatin and/or doxorubicin. The patients received graded doses of dexamethasone phosphate, in the range 40-200 mg, dependent upon nausea and vomiting scores, during up to three consecutive cycles of cancer chemotherapy. Plasma and urine concentrations of dexamethasone (dexamethasone alcohol) were measured by HPLC. The plasma concentration - time data were described by an open two-compartment model. The pharmacokinetic variables were independent of the dose of dexamethasone over the range studied. The terminal half-time was 4.0 +/- 0.4 h and the total body clearance was 3.5 +/- 0.4 ml X min-1 X kg-1. The volume of the central compartment and the total apparent volume of distribution were 0.23 +/- 0.03 and 1.0 +/- 0.1 l X kg-1 respectively. Approximately 8% of the dose was excreted into the urine as dexamethasone.
Topics: Aged; Dexamethasone; Half-Life; Humans; Middle Aged; Neoplasms
PubMed: 3653229
DOI: 10.1007/BF02455994 -
Pflugers Archiv : European Journal of... May 1998Catecholamines have been implicated in neuromodulation of peripheral chemosensitivity and central respiratory mechanisms. Because glucocorticoids can affect...
Catecholamines have been implicated in neuromodulation of peripheral chemosensitivity and central respiratory mechanisms. Because glucocorticoids can affect catecholamine metabolism in the carotid body and brainstem, this study explored the possibility that, in rats, dexamethasone or adrenalectomy affects catecholamine biosynthesis in carotid body chemoreceptors and the medullary areas (A2C2, A5, A6, A7) involved in the chemoreflex pathway and the hypoxic ventilatory response (HVR). One dexamethasone injection (1 mg/kg body wt.) stimulated tyrosine hydroxylase activity in the carotid body and had no effect in brainstem catecholamine areas, while HVR was reduced. Chronic dexamethasone (1 mg/kg body wt. daily for 10 days) had a stimulatory influence on tyrosine hydroxylase activity in the carotid body and an inhibitory effect on A2C2, A5 and A7 cell groups. Breathing pattern, but not HVR, was altered. Adrenalectomy elicited an increase in tyrosine hydroxylase activity in A2C2, which was accompanied by a decreased respiratory frequency in hypoxia. The data show that glucocorticoids have differential effects on catecholamine biosynthesis in peripheral and central structures involved in the chemoreflex pathway. Depending on the treatment, the neurochemical changes were accompanied by alterations of HVR or the breathing pattern, which are consistent with a neuromodulating influence of catecholamines on peripheral chemosensory inputs or the central respiratory network.
Topics: Adrenalectomy; Animals; Brain Stem; Carotid Body; Chemoreceptor Cells; Dexamethasone; Glucocorticoids; Hypoxia; Male; Medulla Oblongata; Rats; Rats, Sprague-Dawley; Respiration; Tyrosine 3-Monooxygenase
PubMed: 9518513
DOI: 10.1007/s004240050591 -
Microvascular Research Sep 1989We examined the effect of dexamethasone (DXM) pretreatment on microvascular transport of macromolecules in ischemia-reperfusion injury. The rat cremaster muscle was...
We examined the effect of dexamethasone (DXM) pretreatment on microvascular transport of macromolecules in ischemia-reperfusion injury. The rat cremaster muscle was splayed, placed in a Lucite intravital chamber, and suffused with bicarbonate buffer. The clearance of fluorescein isothiocyanate-dextran 150 (FITC-Dx 150) was measured as an index of microvascular transport. After determination of baseline data, the muscle was made ischemic for 2 hr by clamping its vascular pedicle, and subsequently reperfused for 2 hr. Ischemia-reperfusion produced a marked increase in clearance of FITC-Dx 150. After an initial peak of 13 times baseline value clearance fell to approximately 4 times baseline level 30 min into the reperfusion period. Clearance increased slowly throughout the remainder of the experiment, reaching 6 times baseline after 2 hr of reperfusion. The treated animals received DXM 3 hr prior to and immediately preceding the pedicle clamping. DXM reduced macromolecular clearance significantly after the first 30 min of reperfusion, and prevented the increase in clearance over time. After an initial peak, clearance values fell to near twice baseline in DXM-treated animals, and remained at this level for the 2 hr of reperfusion. Our data demonstrate that DXM attenuates the alternations in microvascular macromolecular transport produced by ischemia-reperfusion injury.
Topics: Analysis of Variance; Animals; Dexamethasone; Male; Microcirculation; Muscles; Rats; Rats, Inbred WF; Reperfusion Injury
PubMed: 2796761
DOI: 10.1016/0026-2862(89)90024-1 -
Zhonghua Nei Ke Za Zhi Nov 2022
Topics: Humans; Hyperaldosteronism; Adrenocorticotropic Hormone; Dexamethasone; Hydrocortisone; Aldosterone
PubMed: 36323574
DOI: 10.3760/cma.j.cn112138-20211219-0089