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Respiratory Investigation Jul 2023Dexamethasone, remdesivir, and baricitinib reduce mortality in patients with coronavirus disease 2019 (COVID-19). A single-arm study using combination therapy with all...
Combination therapy with predicted body weight-based dexamethasone, remdesivir, and baricitinib in patients with COVID-19 pneumonia: A single-center retrospective cohort study during 5th wave in Japan.
BACKGROUND
Dexamethasone, remdesivir, and baricitinib reduce mortality in patients with coronavirus disease 2019 (COVID-19). A single-arm study using combination therapy with all three drugs reported low mortality in patients with severe COVID-19. In this clinical setting, whether dexamethasone administered as a fixed dose of 6 mg has sufficient inflammatory modulation effects of reducing lung injury has been debated.
METHODS
This single-center retrospective study was conducted to compare the treatment strategies/management in different time periods. A total of 152 patients admitted with COVID-19 pneumonia who required oxygen therapy were included in this study. A predicted body weight (PBW)-based dose of dexamethasone with remdesivir and baricitinib was administered between May and June 2021. After this period, patients were administered a fixed dose of dexamethasone at 6.6 mg/day between July and August 2021. The additional respiratory support frequency of high-flow nasal cannula, noninvasive ventilation, and mechanical ventilation was analyzed. Moreover, the Kaplan-Meier method was used to analyze the duration of oxygen therapy and the 30-day discharge alive rate, and they were compared using the log-rank test.
RESULTS
Intervention and prognostic comparisons were performed in 64 patients with PBW-based and 88 with fixed-dose groups. The frequency of infection or additional respiratory support did not differ statistically. The cumulative incidence of being discharged alive or oxygen-free rate within 30 days did not differ between the groups.
CONCLUSIONS
In patients with COVID-19 pneumonia who required oxygen therapy, combination therapy with PBW-based dexamethasone, remdesivir, and baricitinib might not shorten the hospital stay's length or oxygen therapy's duration.
Topics: Humans; COVID-19; Retrospective Studies; SARS-CoV-2; Japan; COVID-19 Drug Treatment; Dexamethasone
PubMed: 37119744
DOI: 10.1016/j.resinv.2023.03.009 -
Molecules (Basel, Switzerland) Apr 2015In order to investigate the pharmacokinetics of a combination of diazepam and dexamethasone under hypoxic conditions, a novel, sensitive and specific liquid... (Comparative Study)
Comparative Study
Simultaneous Quantification of Diazepam and Dexamethasone in Plasma by High-Performance Liquid Chromatography with Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Comparison between Normoxic and Hypoxic Rats.
In order to investigate the pharmacokinetics of a combination of diazepam and dexamethasone under hypoxic conditions, a novel, sensitive and specific liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of diazepam and dexamethasone in rat plasma was developed and validated. The chromatographic separation of analytes was successfully achieved on an XTerra® MS C18 column using a gradient elution of methanol and water containing 0.1% formic acid at a flow rate of 0.5 mL/min. This method demonstrated good linearity and no endogenous material interferences. The linear ranges were 1.0-100 ng/mL for diazepam and 2.0-200 ng/mL for dexamethasone. The intra- and inter-day precision for the two compounds in plasma were lower than 10.0%, and the accuracy was between -7.9% and 11.5%. Our method was then successfully applied in a pharmacokinetic comparison between normoxic and hypoxic rats. The results indicated that there were significant differences in the main pharmacokinetics parameters of diazepam and dexamethasone between normoxic and hypoxic rats. The results provide the important and valuable information for discovering and developing novel anti-hypoxia drug combinations, as well as a better understanding of the safety and efficacy of these drugs.
Topics: Animals; Chromatography, High Pressure Liquid; Dexamethasone; Diazepam; Drug Therapy, Combination; Hypoxia; Male; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry
PubMed: 25913929
DOI: 10.3390/molecules20046901 -
The American Journal of Case Reports Apr 2019BACKGROUND Hiccups induced by steroids administration is not common. Although it is not life-threatening and is always recognized as a transient and minor complication,...
BACKGROUND Hiccups induced by steroids administration is not common. Although it is not life-threatening and is always recognized as a transient and minor complication, it can be severely uncomfortable and significantly diminished patient quality of life. In this case report, persistent hiccups were observed in 2 middle-aged Thai men receiving low-dose intravenous dexamethasone. This case report highlights the awareness of severe dexamethasone-induced hiccups. CASE REPORT A 49-year-old man and a 38-year-old man were admitted to our hospital and received IV dexamethasone. The hiccups started after each patient received a single dose of dexamethasone. The frequency and severity of their hiccups increased over time during dexamethasone treatment. Hiccups still continued to occur despite the discontinuation of dexamethasone and lasted for 72 h after drug termination. CONCLUSIONS Dexamethasone can cause persistent hiccups. Although hiccups are not life-threatening, it should not be neglected since it can be severely uncomfortable and significantly diminish patient quality of life. Termination of dexamethasone can gradually relieve hiccups. Dexamethasone should be used cautiously and clinicians must be aware of this undesirable effect.
Topics: Administration, Intravenous; Dexamethasone; Dose-Response Relationship, Drug; Glucocorticoids; Hiccup; Humans; Male; Middle Aged; Severity of Illness Index
PubMed: 31036799
DOI: 10.12659/AJCR.915282 -
Signal Transduction and Targeted Therapy Apr 2022
Topics: Dexamethasone; Humans; Macrophages, Alveolar; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35387969
DOI: 10.1038/s41392-022-00977-1 -
Cellular and Molecular Life Sciences :... Aug 2023The glucocorticoid receptor (GR) is a crucial drug target in multiple myeloma as its activation with glucocorticoids effectively triggers myeloma cell death. However, as...
The glucocorticoid receptor (GR) is a crucial drug target in multiple myeloma as its activation with glucocorticoids effectively triggers myeloma cell death. However, as high-dose glucocorticoids are also associated with deleterious side effects, novel approaches are urgently needed to improve GR action in myeloma. Here, we reveal a functional crosstalk between GR and the mineralocorticoid receptor (MR) that plays a role in improved myeloma cell killing. We show that the GR agonist dexamethasone (Dex) downregulates MR levels in a GR-dependent way in myeloma cells. Co-treatment of Dex with the MR antagonist spironolactone (Spi) enhances Dex-induced cell killing in primary, newly diagnosed GC-sensitive myeloma cells. In a relapsed GC-resistant setting, Spi alone induces distinct myeloma cell killing. On a mechanistic level, we find that a GR-MR crosstalk likely arises from an endogenous interaction between GR and MR in myeloma cells. Quantitative dimerization assays show that Spi reduces Dex-induced GR-MR heterodimerization and completely abolishes Dex-induced MR-MR homodimerization, while leaving GR-GR homodimerization intact. Unbiased transcriptomics analyses reveal that c-myc and many of its target genes are downregulated most by combined Dex-Spi treatment. Proteomics analyses further identify that several metabolic hallmarks are modulated most by this combination treatment. Finally, we identified a subset of Dex-Spi downregulated genes and proteins that may predict prognosis in the CoMMpass myeloma patient cohort. Our study demonstrates that GR-MR crosstalk is therapeutically relevant in myeloma as it provides novel strategies for glucocorticoid-based dose-reduction.
Topics: Humans; Glucocorticoids; Receptors, Mineralocorticoid; Dexamethasone; Multiple Myeloma; Receptors, Glucocorticoid; Spironolactone
PubMed: 37578563
DOI: 10.1007/s00018-023-04900-x -
Journal of Veterinary Internal Medicine May 2021A study reported low systemic availability of injectable dexamethasone nebulized to healthy horses using the Flexineb mask. When used in horses with severe asthma and a...
BACKGROUND
A study reported low systemic availability of injectable dexamethasone nebulized to healthy horses using the Flexineb mask. When used in horses with severe asthma and a different nebulizer, lack of efficacy and cortisol suppression were observed.
HYPOTHESIS
Nebulized dexamethasone is as effective as PO administration for the treatment of severe asthma in horses.
ANIMALS
Twelve horses with severe asthma from a research herd.
METHODS
Randomized clinical trial. Horses were divided into 2 groups and received 5 mg of dexamethasone sodium phosphate by nebulization using a Flexineb mask (NE, n = 6) or PO (OR, n = 6) q24h for 7 days. Lung function and serum cortisol concentrations were evaluated at baseline, after 4 days of treatment (D4) and 1 day after the last treatment (D8). Data were analyzed using linear mixed models with Benjamini-Hochberg adjustments.
RESULTS
Lung resistance significantly improved at D4 (mean decrease ± SD, -1.5 ± 0.45 cm H₂O/L/s; 95% confidence interval [CI], -2; -0.6) and D8 (-1.4 ± 0.45 cm H₂O/L/s; 95% CI, -2.4; -0.5) compared to baseline in the OR group only (P = .004 and .01, respectively). Serum cortisol concentration was significantly decreased at D4 and D8 for both groups (maximum decrease, -1.2 ± 0.3 μg/dL; 95% CI, -1.9; -0.6 at D4 for NE group and -2.2 ± 0.3 μg/dL; 95% CI, -2.8; -1.6 at D8 for OR group; P < .001).
CONCLUSIONS AND CLINICAL IMPORTANCE
Oral, but not nebulized dexamethasone is an effective therapy for horses with severe asthma and both treatment modalities inhibit the hypothalamic-pituitary-adrenal axis.
Topics: Animals; Asthma; Dexamethasone; Horse Diseases; Horses; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System
PubMed: 33817859
DOI: 10.1111/jvim.16113 -
Theranostics 2022Very preterm infants may require dexamethasone (Dex) for facilitating extubation or treating bronchopulmonary dysplasia. However, Dex may result in disturbance of...
Very preterm infants may require dexamethasone (Dex) for facilitating extubation or treating bronchopulmonary dysplasia. However, Dex may result in disturbance of metabolisms. This study was to investigate the effects of postnatal short course Dex exposure on brown adipose tissue (BAT) in neonatal rats. : Neonatal rats received either three consecutive doses of daily Dex (0.2 mg/kg/day) or saline from postnatal P1 to P3. We investigated the effects of Dex on BAT including thermogenesis, mitochondrial dynamics and autophagy flux. We also compared diurnal temperature variation between preterm infants who received systemic corticosteroid and their treatment-naïve controls. : Postnatal Dex treatment induced growth retardation, BAT whitening, UCP1 downregulation and cold intolerance in neonatal rats. BAT mitochondria were damaged, evident by loss of normal number, structure, and alignment of cristae. Mitochondrial fission-fusion balance was disrupted and skewed toward increased fusion, reflected by increased OPA1 and MFN2 and decreased DRP1, FIS1 and phosphorylated MFF protein levels. Autophagosome synthesis was increased but clearance was inhibited, indicated by accumulation of p62 protein after Dex treatment and no further increase of LC3-II after chloroquine co-treatment. While autophagy modulators, including chloroquine and rapamycin, did not improve UCP1 downregulation and BAT whitening, AMPK activators could partially rescue these damages. We also demonstrated that preterm infants had higher diurnal temperature variation during corticosteroid treatment. : Postnatal short course Dex impaired BAT mitochondrial function and autophagy flux in rat pups. AMPK activators had the potential to rescue the damage.
Topics: AMP-Activated Protein Kinases; Adipose Tissue, Brown; Animals; Animals, Newborn; Autophagy; Chloroquine; Dexamethasone; Humans; Infant, Newborn; Infant, Premature; Rats; Thermogenesis
PubMed: 35966581
DOI: 10.7150/thno.70752 -
Journal of Pain and Symptom Management May 2004The delivery of subcutaneous medication by continuous infusion is common in palliative medicine. Many centers combine multiple medications, but the analytical... (Comparative Study)
Comparative Study
The delivery of subcutaneous medication by continuous infusion is common in palliative medicine. Many centers combine multiple medications, but the analytical confirmation of the compatibility and stability of these combinations has rarely been performed. This study examined the compatibility and stability of midazolam and dexamethasone using high performance liquid chromatography. Nine different solutions were prepared in polypropylene syringes by combining these two drugs with 0.9% sodium chloride. When these two drugs were combined in a syringe, there was significant loss of midazolam over 48 hours, with only 60-80% of the initial concentration remaining in syringes stored at 35-39 degrees C. This study demonstrates that cloudiness of a solution is not the only predictor of drug loss and that drug loss may occur even in solutions that remain clear at time of preparation. The clinical implications of these results are that dexamethasone and midazolam should not be combined in syringe driver solutions.
Topics: Analgesics; Antidepressive Agents; Chromatography, High Pressure Liquid; Dexamethasone; Drug Combinations; Drug Compounding; Drug Incompatibility; Drug Stability; Drug Storage; Infusions, Parenteral; Injections, Subcutaneous; Midazolam; Palliative Care; Solutions; Syringes
PubMed: 15120775
DOI: 10.1016/j.jpainsymman.2004.02.002 -
Drug Delivery Dec 2021With dexamethasone as the model drug and polycaprolactone (PCL) as the carrier material, a drug delivery coating for cochlear electrodes was prepared, to control...
With dexamethasone as the model drug and polycaprolactone (PCL) as the carrier material, a drug delivery coating for cochlear electrodes was prepared, to control cochlear fibrosis caused by cochlear implantation. A dexamethasone/poly (ε-caprolactone)-based electrode coating was prepared using the impregnation coating method. Preparation parameters were optimized, yielding 1 impregnation instance, impregnation time of 10 s, and PCL concentration of 10%. The coating was characterized using scanning electron microscopy, a universal machine, high-performance liquid chromatography, and CCK-8. The surface was porous and uniformly thick (average thickness, 48.67 µm)-with good flexibility, long-term slow drug release, and optimal drug concentration-and was biologically safe. The experimental results show that PCL is an ideal controlled-release material for dexamethasone as a drug carrier coating for cochlear implants.
Topics: Animals; Anti-Inflammatory Agents; Biocompatible Materials; Cochlear Implants; Delayed-Action Preparations; Dexamethasone; Dose-Response Relationship, Drug; Fibrosis; Polyesters; Porosity; Rats; Surface Properties
PubMed: 34347538
DOI: 10.1080/10717544.2021.1960927 -
Pain Physician Jan 2024Epidural steroid injections are widely used to treat spinal and radiating pain. However, crystal formation has recently been reported in mixtures of ropivacaine and...
BACKGROUND
Epidural steroid injections are widely used to treat spinal and radiating pain. However, crystal formation has recently been reported in mixtures of ropivacaine and nonparticulate steroids, commonly used in epidural steroid injections.
OBJECTIVES
Our study assessed the physicochemical stability of mixtures of different nonparticulate steroids and ropivacaine and aimed to propose a safe regimen for epidural steroid injections.
STUDY DESIGN
An in vitro protocol was used to examine the physicochemical stability of epidural steroid injection mixtures most commonly used at our institution.
SETTING
In vitro laboratory study.
METHODS
Twelve solutions were prepared by mixing 0.75% or 0.2% ropivacaine with dexamethasone or betamethasone at volume ratios of 1:1, 2:1, and 3:1 in propylene syringes at 24°C. The physical properties of the mixtures were observed with the naked eye and under a microscope, and their pH was measured. The concentration of each drug in the mixture was evaluated using high-performance liquid chromatography.
RESULTS
None of the ropivacaine and dexamethasone mixtures showed macroscopic or microscopic crystal formation after 2 hours, and there were no significant changes in pH. The concentrations of the 2 drugs remained stable for up to 2 hours. In contrast, at least 10 mu-m crystals were observed microscopically and macroscopically in all mixtures of ropivacaine and betamethasone; the ropivacaine concentration was reduced by > 10% after one hour.
LIMITATIONS
Confirming the stability of drugs in vitro does not ensure that their pharmacokinetics and pharmacodynamics remain unaltered in vivo.
CONCLUSION
The combination of ropivacaine and betamethasone should be avoided because of their physicochemical instability. Combinations of ropivacaine and dexamethasone should be administered cautiously because they are more physicochemically stable than combinations of ropivacaine and betamethasone.
Topics: Humans; Ropivacaine; Betamethasone; Research Design; Pain; Dexamethasone
PubMed: 38285041
DOI: No ID Found