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Experimental Cell Research Feb 2020The aim of this study is to establish the dexamethasone sodium phosphate multivesicular liposomes thermosensative hydrogel (DEX-MVLs-Gel) drug delivery system and to...
OBJECTIVE
The aim of this study is to establish the dexamethasone sodium phosphate multivesicular liposomes thermosensative hydrogel (DEX-MVLs-Gel) drug delivery system and to analyze the pharmacodynamics, pharmacokinetics and safety of DEX-MVLs-Gel as well as to explore whether the prepared DEX-MVLs-Gel can protect the hearing in the guinea pigs following noise exposure.
METHODS
DEX-MVLs formulations were constructed by double emulsion method, and the DEX-MVLs-Gel was prepared after adding P407 and P188 into the DEX-MVLs. A total of 20 adult albino guinea pigs were chosen to establish the animal models with noise-induced hearing loss. After animals were treated with DEX-MVLs-Gel at concentrations of 20, 6 and 2 mg/mL, and 5 mg/mL Dexamethasone Sodium Phosphate (DEX-P) solution, respectively, the hearing function, drug concentration in the peripheral lymph fluid, and hair cell morphology were assessed.
RESULTS
The ABR threshold of the 20 mg/mL DEX-MVLs-Gel treated group at the frequencies of 4, 8, 16 and 24 kHz were measured as 47.5 ± 5.2, 48.3 ± 4.1, 55.8 ± 3.8 and 57.5 5 ± 5.2 dB SPL, respectively. Statistical significances were noted between the 20 mg/mL DEX-MVLs-Gel treated group and control group at each frequency (all P < 0.05), between the 2 mg/mL and 6 mg/mL DEX-MVLs-Gel treated groups at the frequencies of 4 and 8 kHz (both P < 0.05). High Performance Liquid Chromatography (HPLC) demonstrated that the drug concentrations in the peripheral lymph in all groups were gradually decreased on the 1st, 3rd and 7th d after intratympanic injection. Scattered hair cell loss could be observed mainly in the basal and middle turn in the saline administrated group and the 20 mg/mL DEX-MVLs-Gel administration group, and the hair cell loss was not identified in the apical turn.
CONCLUSIONS
A high concentration (20 mg/mL) of DEX-MVLs-Gel exerts significant protective effects upon the guinea pigs with noise-induced hearing loss. The prepared DEX-MVLs-Gel can be effectively maintained in the peripheral lymph fluid of guinea pigs for 3-7 d and MVLs-Gel causes no obvious ototoxicity.
Topics: Animals; Dexamethasone; Guinea Pigs; Hearing Loss, Noise-Induced; Hydrogels; Liposomes; Models, Animal
PubMed: 31812471
DOI: 10.1016/j.yexcr.2019.111755 -
Journal of Pediatric Gastroenterology... Oct 2002Early postnatal glucocorticoid exposure accelerates the maturation of the bowel mucosa but results in bowel wall thinning in the newborn mouse ileum and increases the...
BACKGROUND
Early postnatal glucocorticoid exposure accelerates the maturation of the bowel mucosa but results in bowel wall thinning in the newborn mouse ileum and increases the risk of focal ileal perforation in extremely premature infants. We have previously demonstrated a redistribution of insulin-like growth factor-I (IGF-I) from the submucosa in control animals to the distal villi of those treated with early postnatal dexamethasone, implicating IGF-I as an important mediator of dexamethasone's capacity to alter tissue growth. To investigate the possibility that IGF binding proteins (IGFBPs) might contribute to this process, we characterized the localization and abundance of IGFBP peptides and mRNAs in the same model.
METHODS
Newborn mice received daily intraperitoneal injections of dexamethasone (l microg/g) or phosphate-buffered saline and then were euthanized on day 3 of life. Their ileums were harvested and prepared for microscopy. Tissue sections of ileum from both treatment conditions were processed in parallel for immunolocalization of each of the six IGFBP peptides and for in situ hybridization of each of the six IGFBP transcripts.
RESULTS
Transcripts for IGFBP-1, -2, and -3 were highly abundant and ubiquitous the ileal mucosa, whereas transcripts for IGFBP-4, -5, and -6 were less abundant in epithelial cells. There were no differences in abundance between control and dexamethasone-treated ileum with regard to mRNA localization or abundance for IGFBP-1, -2, -3, and -6. In contrast, mRNA transcripts for IGFBP-4 and -5 were modestly increased with dexamethasone treatment (although only IGFBP-4 was significant). Strikingly different patterns of IGFBP immunolocalization were observed between control and dexamethasone-treated animals. IGFBP-1, -2, -3, and -5 were not detected in control ileum, whereas IGFBP-4 and -6 were both present in the mucosa. In contrast, dexamethasone treatment resulted in dramatic mucosal increases in IGFBP-2, -3, -4, and -5, paralleling the changing distribution of IGF-I that we previously reported.
CONCLUSION
Taken together, these findings further implicate the IGF system as an important participant in dexamethasone-induced maturation in the newborn mouse ileum.
Topics: Animals; Animals, Newborn; Dexamethasone; Disease Models, Animal; Ileum; Immunohistochemistry; In Situ Hybridization; Insulin-Like Growth Factor Binding Proteins; Intestinal Mucosa; Mice; RNA, Messenger
PubMed: 12394380
DOI: 10.1097/00005176-200210000-00014 -
Klinische Padiatrie 1989Dexamethasone has recently been introduced for the treatment of bronchopulmonary dysplasia (BPD). Whereas the short-term effect of dexamethasone has been documented in...
Dexamethasone has recently been introduced for the treatment of bronchopulmonary dysplasia (BPD). Whereas the short-term effect of dexamethasone has been documented in previous publications, studies on the long-term effect do not appear to exist in the literature. The aim of this retrospective study was to investigate the influence of dexamethasone on respiratory parameters, the long-term efficacy, and the side-effects. Dexamethasone was given to premature babies with BPD who could not be weaned from the respirator. Twelve infants were included in this study. The gestational ages ranged from 26 to 30 weeks and the birth weights ranged from 640 to 1410 g. Dexamethasone treatment was initiated at the age of 14 to 44 days. After 6 days of dexamethasone therapy, ventilation rates and FiO2 values improved significantly. All infants were successfully weaned from mechanical ventilation and extubated at 2 to 40 days after the start of dexamethasone therapy. The follow-up for the estimation of the long-term efficacy ranged from 3 to 18 months. Ten out of twelve patients had been weaned permanently from the ventilator; one 12-months-old infant is still respirator-dependent. One patient died at 8 months from BPD. In 5 out of 12 infants we observed a leukocytosis with neither clinical signs nor microbiological signs of an infection. Septicaemia developed in one case and one patient suffered from pneumonia. Arterial hypertension was observed in one infant during dexamethasone therapy. The results suggest that dexamethasone facilitates the weaning of preterm infants with BPD from the ventilator. This treatment may prevent some infants from long-term ventilation.
Topics: Bronchopulmonary Dysplasia; Dexamethasone; Female; Humans; Infant, Newborn; Long-Term Care; Male; Respiration, Artificial
PubMed: 2495383
DOI: 10.1055/s-2007-1025268 -
Acta Anaesthesiologica Scandinavica Feb 2020Multimodal analgesia is considered the leading principle for post-operative pain treatment, but no gold standard after total knee arthroplasty (TKA) exists. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Multimodal analgesia is considered the leading principle for post-operative pain treatment, but no gold standard after total knee arthroplasty (TKA) exists.
AIM
To investigate the beneficial and harmful effects of one or two doses of 24 mg intravenous dexamethasone (DXM) as part of a multimodal analgesic regimen (paracetamol, NSAID and perioperative local infiltration analgesia) after TKA. We hypothesize that addition of DXM will reduce post-operative opioid consumption.
METHODS
DEXamethasone twice for pain treatment after TKA is a randomized, blinded, three-group multicentre clinical trial. Participants will be randomized to one of three groups: placebo, single dose of DXM or two consecutive doses of DXM. Participants, treatment providers and investigators will be blinded to the allocated intervention. The primary outcome is total opioid consumption (units of morphine equivalents) 0-48 hours post-operatively.
INCLUSION CRITERIA
unilateral, primary TKA; age ≥18 years; American Society of Anesthesiologists-Score 1-3; Body Mass Index ≥18 and ≤40; for women-not pregnant; and written informed consent.
EXCLUSION CRITERIA
allergy or contraindications against trial medication; daily use of high dose opioid and/or use of methadone/transdermal opioids; daily use of systemic glucocorticoids; dysregulated diabetes; and patients suffering from alcohol and/or drug abuse. Four-hundred-and-eighty-six eligible participants are needed to detect or discard a difference of 10 mg morphine equivalents 0-48 hours post-operatively maintaining a familywise error rate of 0.05 and a power of 90% for the three possible pairwise comparisons.
DISCUSSION
Recruiting is planned to commence September 2018 and expected to finish March 2020.
TRIAL REGISTRATION
EudraCT: 2018-001099-39 (08/06-18); ClinicalTrials.gov: NCT03506789 (24/04-2019). Editorial Comment This is the protocol for the largest randomized clinical trial investigating the effect of one or two doses of dexamethasones on pain treatment after total knee arthroplasty. Due to the pragmatic and rigerous design this study will deliver results of high quality and external validity.
Topics: Arthroplasty, Replacement, Knee; Clinical Protocols; Dexamethasone; Humans; Pain, Postoperative
PubMed: 31544230
DOI: 10.1111/aas.13481 -
Veterinary Dermatology Apr 2022
Concerns regarding McClintock et al. Oral dexamethasone sodium phosphate solution significantly reduces pruritus and clinical lesions in feline hypersensitivity dermatitis: an open-label study.
Topics: Animals; Cat Diseases; Cats; Dermatitis; Dexamethasone; Hypersensitivity; Pruritus
PubMed: 35312109
DOI: 10.1111/vde.13069 -
Ugeskrift For Laeger Jan 2003
Topics: Adult; Anti-Bacterial Agents; Dexamethasone; Drug Therapy, Combination; Glucocorticoids; Humans; Meningitis, Bacterial
PubMed: 12555711
DOI: No ID Found -
The Annals of Pharmacotherapy Sep 1994Premature neonates with bronchopulmonary dysplasia frequently are treated with intravenous dexamethasone for their chronic lung disease. The injection volumes of the... (Comparative Study)
Comparative Study
OBJECTIVE
Premature neonates with bronchopulmonary dysplasia frequently are treated with intravenous dexamethasone for their chronic lung disease. The injection volumes of the commercially available products often are too small to measure accurately. The objective of this study was to evaluate the stability over 28 days of dexamethasone sodium phosphate injection 4 mg/mL diluted with bacteriostatic NaCl 0.9% to 1 mg/mL.
DESIGN
Ten vials of dexamethasone 1 mg/mL were prepared from dexamethasone sodium phosphate injection, USP 4 mg/mL and bacteriostatic NaCl 0.9% injection. Five vials were stored at 4 degrees C and five at 22 degrees C. Dexamethasone was measured on days 0, 1, 3, 7, 14, 21, and 28 by an accurate, reproducible, and stability-indicating HPLC method. Samples were also inspected visually for precipitation or discoloration on each study day.
RESULTS
The samples retained at least 97.7 percent of the original concentration of dexamethasone sodium phosphate when stored at either 4 or 22 degrees C for 28 days. No discoloration or precipitation was observed.
CONCLUSIONS
Dexamethasone sodium phosphate injection 1 mg/mL in bacteriostatic NaCl 0.9% was stable for 28 days at 4 and 22 degrees C.
Topics: Chromatography, High Pressure Liquid; Dexamethasone; Drug Stability; Humans; Injections, Intravenous; Sodium Chloride; Temperature; Time Factors
PubMed: 7803873
DOI: 10.1177/106002809402800903 -
Hand Surgery & Rehabilitation Dec 2021Digital nerve block is one of the multimodal analgesia methods used in finger trauma cases. According to some studies, dexamethasone needs further investigation before... (Randomized Controlled Trial)
Randomized Controlled Trial
Digital nerve block is one of the multimodal analgesia methods used in finger trauma cases. According to some studies, dexamethasone needs further investigation before being used routinely. We therefore investigated dexamethasone's effect on the parameters of digital nerve block. In this double-blind clinical study, 60 patients were allocated to two groups: lidocaine alone and lidocaine + dexamethasone. Groups were compared for pain intensity, analgesia duration and demographic characteristics. Patients in the intervention group received 3 cc 2% lidocaine + 1 cc (equivalent to 4 mg) dexamethasone and patients in the control group received 3 cc lidocaine 2% + 1 cc normal saline. The two groups were comparable for age and gender. In the lidocaine + dexamethasone group, postoperative pain severity was significantly lower and the pain-free period was longer (P < 0.05). Dexamethasone as an adjuvant in digital nerve block after trauma reduced the severity of postoperative pain and increased the pain-free period.
Topics: Analgesia; Anesthetics, Local; Dexamethasone; Humans; Lidocaine; Nerve Block; Pain Measurement
PubMed: 34438110
DOI: 10.1016/j.hansur.2021.08.007 -
Pharmacotherapy 1998To assess the potential for a drug-drug interaction between valspodar, a P-glycoprotein (mdrl) modulator used as a chemotherapy adjunct, and dexamethasone, widely... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
STUDY OBJECTIVE
To assess the potential for a drug-drug interaction between valspodar, a P-glycoprotein (mdrl) modulator used as a chemotherapy adjunct, and dexamethasone, widely included in oncology antiemetic regimens.
DESIGN
Randomized, open-label, three-period crossover study.
SETTING
Clinical pharmacology research center.
SUBJECTS
Eighteen healthy men volunteers (age 25.8+/-3.5 yrs, weight 71.6+/-10.3 kg).
INTERVENTIONS
Subjects received single fasting oral doses of valspodar 400 mg, dexamethasone 8 mg, and both drugs concomitantly with 2- to 3-week washout phases between administrations.
MEASUREMENTS AND MAIN RESULTS
Lack of a pharmacokinetic drug-drug interaction with respect to valspodar was conclusively demonstrated for both Cmax,b (2.3+/-0.4 vs 2.4+/-0.5 microg/ml) and AUCb (19.8+/-4.8 vs 19.6+/-4.9 microg x hr/ml) inasmuch as bioequivalence criteria were satisfied when comparing administration alone with coadministration, respectively. Although no changes in the rate of dexamethasone absorption were noted on coadministration with valspodar (Cmax 88+/-23 vs 91+/-20 ng/ml), overall exposure was significantly increased by 24% on average (AUC 400+/-87 vs 494+/-90 ng x hr/ml). Regression analysis of valspodar Cmax,b and AUCb during coadministration versus the extent of the interaction (percentage increase in dexamethasone AUC) did not reveal a concentration-effect relationship (p=0.7299 and 0.9718, respectively).
CONCLUSION
Given dexamethasone's wide therapeutic index and the short duration of coadministration foreseen for these drugs in a clinical setting (maximum 1 wk/chemotherapy cycle), the 24% increase in dexamethasone's AUC is unlikely to be relevant. Thus no alterations in valspodar or dexamethasone dosages appear warranted when the two drugs are coadministered. Multiple-dose experience in patients would be desirable to confirm these conclusions.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Adult; Antiemetics; Area Under Curve; Cross-Over Studies; Cyclosporins; Dexamethasone; Drug Interactions; Extremities; Humans; Linear Models; Male; Paresthesia
PubMed: 9855321
DOI: No ID Found -
Cancer Chemotherapy and Pharmacology 1981Severe, debilitating nausea and vomiting are seen in almost 100% of patients treated with cis-platinum. These side-effects can be so severe and prolonged as to preclude...
Severe, debilitating nausea and vomiting are seen in almost 100% of patients treated with cis-platinum. These side-effects can be so severe and prolonged as to preclude therapy in a large number of patients. Commonly used antiemetics have had only limited success in controlling cis-platinum-induced nausea and vomiting. Various reports have indicated benefits from steroids in this setting. We have tested a high-dose dexamethasone regimen with or without neuroleptics, which inhibits chemotherapy-induced vomiting in 50% of patients failing with prior antiemetics and in 71% of those who had not received prior antiemetics. This treatment was administered on an out-patient basis as it involved oral administration of the antiemetic. Neuroleptic therapy was not randomly assigned, but the results of this pilot study suggest that it did not enhance dexamethasone's efficacy. There were no significant side-effects due to the steroids. The antiemetic effectiveness of dexamethasone was retained through repeated courses of chemotherapy.
Topics: Adult; Aged; Antineoplastic Agents; Antipsychotic Agents; Cisplatin; Dexamethasone; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nausea; Vomiting
PubMed: 6122510
DOI: 10.1007/BF00258206