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Letters in Applied Microbiology Oct 2023This study evaluated the antibiofilm activity of promethazine, deferiprone, and Manuka honey against Staphylococcus aureus and Pseudomonas aeruginosa in vitro and ex...
This study evaluated the antibiofilm activity of promethazine, deferiprone, and Manuka honey against Staphylococcus aureus and Pseudomonas aeruginosa in vitro and ex vivo in a wound model on porcine skin. The minimum inhibitory concentrations (MICs) and the effects of the compounds on biofilms were evaluated. Then, counting colony-forming units (CFUs) and confocal microscopy were performed on biofilms cultivated on porcine skin for evaluation of the compounds. For promethazine, MICs ranging from 97.66 to 781.25 µg/ml and minimum biofilm eradication concentration (MBEC) values ranging from 195.31 to 1562.5 µg/ml were found. In addition to reducing the biomass of both species' biofilms. As for deferiprone, the MICs were 512 and >1024 µg/ml, the MBECs were ≥1024 µg/ml, and it reduced the biomass of biofilms. Manuka honey had MICs of 10%-40%, MBECs of 20 to >40% and reduced the biomass of S. aureus biofilms only. Concerning the analyses in the ex vivo model, the compounds reduced (P < .05) CFU counts for both bacterial species, altering the biofilm architecture. The action of the compounds on biofilms in in vitro and ex vivo tests raises the possibility of using them against biofilm-associated wounds. However, further studies are needed to characterize the mechanisms of action and their effectiveness on biofilms in vivo.
Topics: Animals; Swine; Staphylococcus aureus; Promethazine; Deferiprone; Honey; Biofilms; Pseudomonas aeruginosa; Anti-Bacterial Agents; Microbial Sensitivity Tests
PubMed: 37791895
DOI: 10.1093/lambio/ovad119 -
Biomedicines Aug 2023Molnupiravir is an antiviral drug against viral RNA polymerase activity approved by the FDA for the treatment of COVID-19, which is metabolized to...
Development and Validation of a High-Performance Liquid Chromatography with Tandem Mass Spectrometry (HPLC-MS/MS) Method for Quantification of Major Molnupiravir Metabolite (β-D-N4-hydroxycytidine) in Human Plasma.
Molnupiravir is an antiviral drug against viral RNA polymerase activity approved by the FDA for the treatment of COVID-19, which is metabolized to β-D-N4-hydroxycytidine (NHC) in human blood plasma. A novel method was developed and validated for quantifying NHC in human plasma within the analytical range of 10-10,000 ng/mL using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) to support pharmacokinetics studies. For sample preparation, the method of protein precipitation by acetonitrile was used, with promethazine as an internal standard. Chromatographic separation was carried out on a Shim-pack GWS C18 (150 mm × 4.6 mm, 5 μm) column in a gradient elution mode. A 0.1% formic acid solution in water with 0.08% ammonia solution (eluent A, /) and 0.1% formic acid solution in methanol with 0.08% ammonia solution mixed with acetonitrile in a 4:1 ratio (eluent B, /) were used as a mobile phase. Electrospray ionization (ESI) was used as an ionization source. The developed method was validated in accordance with the Eurasian Economic Union (EAEU) rules, based on the European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines for the following parameters and used within the analytical part of the clinical study of molnupiravir drugs: selectivity, suitability of standard sample, matrix effect, calibration curve, accuracy, precision, recovery, lower limit of quantification (LLOQ), carryover, and stability.
PubMed: 37760797
DOI: 10.3390/biomedicines11092356 -
Substance Abuse : Research and Treatment 2023The substance combination of codeine and promethazine, commonly termed /, has been identified as a method that some individuals use to cope with PTSD and other mental...
The substance combination of codeine and promethazine, commonly termed /, has been identified as a method that some individuals use to cope with PTSD and other mental health symptomology. A sample of 1423 adults with self-reported past year lean use was recruited from substance-related Reddit pages to complete a survey about lean, including information about using lean to cope with emotions, thoughts, or feelings. To be included in the sample, persons needed to: (1) be ⩾18 years old, (2) report past year lean use, (3) complete lean use screeners, and (4) pass data quality checks (eg, bot detection). As Reddit is an online forum, no geographic restrictions were placed on study participation. Data on demographic characteristics, lean use, and mental health disorder symptomology were captured from participants. Logistic regression models included anxiety, depression, and trauma as independent variables along with covariates to examine using lean to cope with emotions, thoughts, or feelings in the past 30 days. Most participants were male (n = 1102; 77.4%), with an average age of 26.9 (SD = 5.2) years. Most participants used included codeine as an ingredient in lean (n = 1060; 74.5%); promethazine was added as an ingredient by 31.7% of the sample (n = 451), and the combination of codeine and promethazine was included as ingredients by 13.5% (n = 192) of the sample. Participants with anxiety, lifetime trauma exposure, and who were female had increased odds of using lean to cope with emotions, thoughts, or feelings in the past 30 days. Those with depression and unstable housing exhibited decreased odds of using lean to cope with emotions, thoughts, or feelings in the past 30 days. This study recruited persons via social media to learn more about lean use, especially lean use to cope with mental health symptoms; future population-level studies are needed.
PubMed: 37746632
DOI: 10.1177/11782218231195226 -
Journal of Nepal Health Research Council Sep 2023Photosensitivity is the response of drug or drug product to the exposure of solar, UV and visible light in the solid, semisolid, or liquid state that leads to a physical...
BACKGROUND
Photosensitivity is the response of drug or drug product to the exposure of solar, UV and visible light in the solid, semisolid, or liquid state that leads to a physical or chemical change. Exposure to light is a concern with numerous medications due to the potential for photo degradation or other chemical reactions that affect drug stability.
METHODS
Out of all the registered brands in Department of Drug Administration, 9 brands of Rabeprazole tablets, 5 brands of Promethazine tablets and 5 brands of methylcobalamin tablets were selected and were subjected for testing and analysis for various quality parameters as per pharmacopoeia. The labels of the collected medicine were analyzed. The obtained data were entered and analyzed in Microsoft office excel 2019.
RESULTS
Eleven products did not comply with the existing regulatory requirement on labeling system of medicine as per Regulation of Standard of drugs. There was no uniformity in mentioning the self-life. Similarly, large variation was seen on price of same generic drugs. Information regarding storage conditions, direction for use and category of the drug were lacking in the label of some brands of medicines.Upon Laboratory analysis, two brands of promethazine tablets and three brands of Rabeprazole tablets were found substandard. Drug content of all the brands of Methylcobalamin was found to contain overage.
CONCLUSIONS
The result of this study indicates that substandard medicines are abundant in Nepalese market. There is weak regulation monitoring which have resulted in no uniformity in similar pharmaceutical products too. Hence, stringent regulatory monitoring is required to assessthe quality of pharmaceutical products in the Nepalese market.
PubMed: 37742143
DOI: 10.33314/jnhrc.v21i1.4131 -
Pediatric Cardiology Jan 2024Delirium is a common postoperative complication in children with congenital heart disease, which affects their postoperative recovery. The purpose of this study is to...
Delirium is a common postoperative complication in children with congenital heart disease, which affects their postoperative recovery. The purpose of this study is to explore the risk factors of delirium and construct a nomogram model to provide novel references for the prevention and management of postoperative delirium in children with congenital heart disease. 470 children after congenital heart surgery treated in the cardiac intensive care unit (CICU) of Shanghai Children's Medical Center were divided into a model and a validation cohort according to the principle of 7:3 distribution temporally. Then, the delirium-related influencing factors of 330 children in the training cohort were analyzed, and the nomogram model was established by a combination of Lasso regression and logistic regression. The data of 140 children in the validation cohort were used to verify the effectiveness of the model. Multivariable logistic regression analysis showed that age, disease severity, non-invasive ventilation after extubation, delayed chest closure, phenobarbital dosage, promethazine dosage, mannitol usage, and elevated temperature were independent risk factors for postoperative delirium. The area under the receiver operating characteristic curve (AUC) of the nomogram model was 0.864 and the Brier value was 0.121. Regarding the validation of the model's effect, our results showed that 51 cases were predicted by the model and 34 cases actually occurred, including 4 cases of false negative and 21 cases of false positive. The positive predictive value of the model was 58.8%, and its negative predictive value was 95.5%. The nomogram model established in this study showed acceptable performance in predicting postoperative delirium in children with congenital heart disease.
Topics: Child; Humans; Emergence Delirium; Prospective Studies; Nomograms; China; Heart Defects, Congenital; Risk Factors; Retrospective Studies
PubMed: 37741935
DOI: 10.1007/s00246-023-03297-5 -
Cureus Aug 2023Public health efforts to reduce the opioid overdose epidemic and treat opioid use disorder (OUD) have met with challenges associated with current non-standardized... (Review)
Review
Public health efforts to reduce the opioid overdose epidemic and treat opioid use disorder (OUD) have met with challenges associated with current non-standardized approaches to managing opioid withdrawal symptoms, such as itching, jitteriness, anxiety, depression, craving, vomiting, diarrhea, insomnia, and anorexia. These symptoms pose substantial obstacles to the safe initiation of medications for OUD, maintenance of long-term sobriety, and prevention of relapse. In clinical practice, multiple medications (polypharmacy) are prescribed to manage these withdrawal symptoms, including ondansetron and promethazine for vomiting and nausea, loperamide and Lomotil for diarrhea, hydroxyzine and doxepin for pruritus, benzodiazepines, the Z-drugs, and melatonin for insomnia, and benzos, tricyclic antidepressants (TCAs), and various serotonergic agents for anxiety. This polypharmacy is associated with an increased risk of adverse drug-drug interactions and adverse drug events, increased medical costs, and increased odds of medication non-adherence and relapse. We propose an alternative single medication, mirtazapine, a noradrenergic and specific serotonergic receptor antagonist, that can be used for myriad symptoms of opioid withdrawal. Case series, clinical studies, and clinical trials have shown mirtazapine to be effective for treating nausea and vomiting resulting from multiple etiologies, including hyperemesis gravidarum and chemotherapy-induced emesis. Other evidence supports the salutary effects of mirtazapine on itching and craving. Research findings support mirtazapine's beneficial effects on diarrhea and anxiety, a consequence of its modulating effects on serotonergic receptors mediating mood and gastrointestinal symptoms. There is also evidence supporting its efficacy as a potent and non-addictive sleep aid, which presents itself as a solution for insomnia associated with opioid withdrawal. The current review presents evidence from extant literature supporting mirtazapine as a one-drug strategy to treat the variety of symptoms of opioid withdrawal. This one-drug strategy has much potential to decrease polypharmacy, adverse drug events, relapse, and healthcare cost and increase the likelihood of prolonged sobriety and better quality of life for people living with OUD.
PubMed: 37736438
DOI: 10.7759/cureus.43821 -
European Clinical Respiratory Journal 2023Sedating antihistamines such as promethazine are used as anxiolytics and hypnotic agents for patients with chronic obstructive pulmonary disease (COPD) with and without...
BACKGROUND
Sedating antihistamines such as promethazine are used as anxiolytics and hypnotic agents for patients with chronic obstructive pulmonary disease (COPD) with and without asthma despite limited knowledge of its effects and side effects. We evaluated if treatment with promethazine had a lower risk of harmful outcome.
METHODS
Nationwide retrospective cohort study of Danish specialist diagnosed outpatients with COPD treated with promethazine or an active comparator (melatonin). Patients with collection of promethazine or melatonin were propensity score matched 1:1. The primary outcome was a composite of severe COPD exacerbations and death from all causes analyzed by Cox proportional hazards regression. We performed an interaction analysis for comorbid asthma.
RESULTS
In our registry of 56,523 patients with COPD, 5,661 collected promethazine ( = 3,723) or melatonin ( = 1,938). A cohort of 3,290 promethazine- or melatonin-treated patients matched 1:1 was available for the primary analysis.Within 1-year patients treated with promethazine were at higher risk of the primary outcome than matched controls with a Hazard Ratio (HR) of 1.42 (CI 1.27-1.58, < 0.0001). Similarly, the risk of death was higher for promethazine-treated patients (HR 1.53, CI 1.32-1.77, < 0.0001). An interaction analysis for comorbid asthma showed no interaction between comorbid asthma and the likelihood of a primary outcome when collecting promethazine ( = 0.19). Adjusted Cox analysis on the entire population indicated a further increased risk with more promethazine (HR for primary outcome among patients collecting ≥ 400 promethazine tablets/year=2.15, CI 1.94-2.38, <0.0001).
CONCLUSIONS
Promethazine-treated patients with COPD had a concerning excess risk of a composite outcome of severe exacerbations and death from all causes compared to melatonin.
PubMed: 37680536
DOI: 10.1080/20018525.2023.2250604 -
Experimental Neurology Nov 2023Neuroprotective effects have been the main focus of new treatment modalities for ischemic stroke. Phenothiazines, or chlorpromazine plus promethazine (C + P), are...
BACKGROUND
Neuroprotective effects have been the main focus of new treatment modalities for ischemic stroke. Phenothiazines, or chlorpromazine plus promethazine (C + P), are known to prevent the generation of free radicals and uptake of Ca by plasma membrane; they have a potential as a treatment for acute ischemic stroke (AIS). This study aims to investigate the role of endoplasmic reticulum (ER) stress-associated PERK-eIF2α pathway underlying the phenothiazine-induced neuroprotective effects after cerebral ischemia/reperfusion (I/R) injury.
METHODS
A total of 49 male Sprague Dawley rats (280-320 g) were randomly divided into 4 groups (n = 7 per group): (1) sham, (2) I/R that received 2 h of middle cerebral artery occlusion (MCAO), followed by 6 or 24 h of reperfusion, (3) MCAO treated by C + P without temperature control and (4) MCAO treated by C + P with temperature control. Human neuroblastoma (SH-SY5Y) cells were used in 5 groups: (1) control, (2) oxygen-glucose deprivation (OGD) for 2 h followed by reoxygenation (OGD/R), (3) OGD/R with C + P; (4) OGD/R with PERK inhibitor, GSK2656157, and (5) OGD/R with C + P and GSK2656157. The molecules of ER stress, unfolded protein response (UPR) (Bip, PERK, p-PERK, p-PERK/PERK, eIF2α, p-eIF2α, p-eIF2α/eIF2α), autophagy (ATG12, LC3II/I), and apoptosis (BAX, Bcl-XL) were measured at mRNA levels by real time PCR and protein levels by Western blotting.
RESULTS
In ischemic rats followed by reperfusion, expression of Bip, p-PERK/PERK, p-eIF2α/eIF2α, ATG12, and LC3II/I, as well as BAX were all significantly increased. These markers were significantly reduced by C + P at both 6 and 24 h of reperfusion. Anti-apoptotic Bcl-XL expression was increased, while pro-apoptotic BAX expression was decreased by C + P. In SH-SY5Y cell lines, both C + P and GSK2656157 significantly reduced the level of autophagy and apoptosis after I/R, respectively. The combination of GSK2656157 and C + P did not promote the same effect, suggesting that C + P did not induce any neuroprotective effect by inhibiting autophagy and apoptosis through the PERK-eIF2α pathway when this pathway was already blocked by GSK2656157. In general, the reduction in body temperature by phenothiazines was associated with better neuroprotection but it did not reach significant levels.
CONCLUSION
The combined treatment of C + P plays a crucial role in stroke therapy by inhibiting ER stress-mediated autophagy, thereby leading to reduced apoptosis and increased neuroprotection. Our findings highlight the PERK-eIF2α pathway as a central mechanism through which C + P exerts its beneficial effects. The results from this study may pave the way for the development of more targeted and effective treatments for stroke patients.
Topics: Animals; Humans; Male; Rats; Apoptosis; Autophagy; bcl-2-Associated X Protein; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Eukaryotic Initiation Factor-2; Infarction, Middle Cerebral Artery; Ischemic Stroke; Neuroblastoma; Neuroprotective Agents; Phenothiazines; Rats, Sprague-Dawley; Reperfusion Injury
PubMed: 37673390
DOI: 10.1016/j.expneurol.2023.114524 -
International Journal of Pharmaceutics Aug 2023We present a physiologically based pharmacokinetic (PBPK) model simulating systemic drug concentrations following administration to the human rectum. Rectum physiology...
We present a physiologically based pharmacokinetic (PBPK) model simulating systemic drug concentrations following administration to the human rectum. Rectum physiology is parameterized based on literature data. The model utilizes in vitro release (IVRT) profiles from which drug mass transfer through the rectal fluid and tissue and into the systemic circulation are predicted. Due to a lack of data, rectal fluid and tissue absorption parameters are predicted either from colon absorption, with modifications relevant to rectal physiology, or optimized. The PBPK model is evaluated by simulating 29 clinical studies for 10 drugs. For 8 drugs (diazepam, diclofenac, indomethacin, naproxen, paracetamol, pentobarbital, phenobarbital and theophylline) the bias (average fold error, AFE) and precision (absolute average fold error, AAFE) of C, AUC and AUC simulations range from 0.87 to 2.22, indicating good agreement with observed values. For prochlorperazine and promethazine, the AFEs and AAFEs of C predictions are 1.30 and 2.52, respectively. TheAUC and AUC are overpredicted for both compounds(AFEs and AAFEs from 2.66 to 4.90). This results from a lack of reliable elimination data for prochlorperazine and the relevance of the IVRT profiles used in the promethazine model. The model paves the way for more mechanistic rectal drug absorption studies and virtual bioequivalence methods for rectal drug products.
Topics: Humans; Pharmaceutical Preparations; Rectal Absorption; Prochlorperazine; Promethazine; Therapeutic Equivalency; Models, Biological; Computer Simulation
PubMed: 37507097
DOI: 10.1016/j.ijpharm.2023.123273 -
Langmuir : the ACS Journal of Surfaces... Aug 2023In the realm of electrochemical sensor application, the development and fabrication of semiconducting metal oxides with the integration of conducting polymers for the...
CdO Decorated with Polypyrrole Nanotube Heterostructure: Potent Electrocatalyst for the Detection of Antihistamine Drug Promethazine Hydrochloride in Environmental Samples.
In the realm of electrochemical sensor application, the development and fabrication of semiconducting metal oxides with the integration of conducting polymers for the trace-level detection of pharmaceutical medicines garnered considerable interest. Herein, we reported facile cadmium oxide decorated with polypyrrole nanotubes fabricated on a glassy carbon electrode (CdO@PPy/GCE) for efficient determination of antihistamine drug promethazine hydrochloride (PMH). The as-synthesized CdO@PPy composite was characterized by various analytical tools like X-ray powder diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. Furthermore, the electrocatalytic activity of the modified electrode for PMH detection was examined by voltammetry and amperometric methods, and the modified electrode exhibited lower charge transfer resistance compared to the bare GCE. Under the optimized condition, the fabricated electrode shows a wide linear range (50-550 μM), better sensitivity (0.13 μAμM cm), low detection limit (10.83 nM) (S/N = 3), and excellent selectivity and reproducibility toward PMH detection. Moreover, the modified GCE depicted eminent practical ability for PMH detection in lake water and pharmaceutical tablets.
Topics: Polymers; Promethazine; Pyrroles; Reproducibility of Results; Nanotubes; Histamine Antagonists; Pharmaceutical Preparations; Electrodes; Limit of Detection
PubMed: 37490749
DOI: 10.1021/acs.langmuir.3c01445