Brompheniramine 12mg modified-release capsules

Pharmaceuticals are receiving increasing attention as emerging contaminants in the aquatic environment. Herein, we investigated the occurrence of 11 antidepressants, 6 antihistamines and 4 metabolites in treated wastewater effluents, rivers, stormwater, and seawater in Hong Kong, with special focus on chirality. The average levels of ∑pharmaceuticals ranged from 0.525 to 1070 ng/L in all samples and the total annual mass load of target pharmaceuticals in the marine environment of Hong Kong was 756 kg/y. Antihistamines accounted for >80 % of ∑pharmaceuticals, with diphenhydramine and fexofenadine being predominant. The occurrence and enantiomeric profiles of brompheniramine and promethazine sulfoxide were reported in global natural waters for the first time. Among chiral pharmaceuticals, mirtazapine and fexofenadine exhibited R-preference, while others mostly exhibited S-preference, implying that the ecological risks derived from achiral data for chiral pharmaceuticals may be biased. The joint probabilistic risk assessment of fluoxetine revealed that R-fluoxetine and rac-fluoxetine presented different ecological risks from that of S-fluoxetine; Such assessment also revealed that target pharmaceuticals posed only minimal to low risks, except that diphenhydramine posed an intermediate risk. As estimated, 10 % aquatic species will be affected when the environmental level of diphenhydramine exceeds 7.40 ng/L, which was seen in 46.9 % samples. Collectively, this study highlights further investigations on the enantioselectivity of chiral pharmaceuticals, particularly on environmental behavior and ecotoxicity using local aquatic species as target organisms.

Abstract licence: CC BY-NC-ND

BACKGROUND: The regulator of calcineurin 1 (RCAN1) is expressed in multiple organs, including the heart, liver, brain, and kidney, and is closely linked to the pathogenesis of cardiovascular diseases, Down syndrome, and Alzheimer's disease. It is also implicated in the development of various organ tumors; however, its potential role in hepatocellular carcinoma (HCC) remains poorly understood. Therefore, the objective of this study was to investigate the potential mechanisms of RCAN1 in HCC through bioinformatics analysis. METHODS: We conducted a joint analysis based on the NCBI and TCGA databases, integrating both bulk transcriptome and single-cell analyses to examine the principal biological functions of RCAN1 in HCC, as well as its roles related to phenotype, metabolism, and cell communication. Subsequently, an RCAN1-overexpressing cell line was established, and the effects of RCAN1 on tumor cells were validated through in vitro experiments. Moreover, we endeavored to identify potential related drugs using molecular docking and molecular dynamics simulations. RESULTS: The expression of RCAN1 was found to be downregulated in 19 types of cancer tissues and upregulated in 11 types of cancer tissues. Higher levels of RCAN1 expression were associated with improved patient survival. RCAN1 was predominantly expressed in hepatocytes, macrophages, endothelial cells, and monocytes, and its high expression not only closely correlated with the distribution of cells related to the HCC phenotype but also with the distribution of HCC cells themselves. Additionally, Rcan1 may directly or indirectly participate in metabolic pathways such as alanine, aspartate, and glutamate metabolism, as well as butanoate metabolism, thereby influencing tumor cell proliferation and migration. In vitro experiments confirmed that RCAN1 overexpression promoted apoptosis while inhibiting proliferation and invasion of HCC cells. Through molecular docking of 1615 drugs, we screened brompheniramine as a potential target drug and verified our results by molecular dynamics. CONCLUSION: In this study, we revealed the relationship between RCAN1 and HCC through bioinformatics methods, verified that RCAN1 can affect the progress of the disease through experiments, and finally identified potential therapeutic drugs through drug molecular docking and molecular dynamics.

Abstract licence: CC BY-NC-ND

A key aspect of pharmaceutical analysis that guarantees the efficacy, safety, and quality of medication items is impurity profiling. It involves the Identification and quantification of Impurities that may arise during synthesis. In this research, a Novel RP-HPLC method was developed and validated, including the separation of Impurities and quantification of Brompheniramine Maleate. The separation of all three main components and Impurities was achieved using Gradient mode with the use of a UV and PDA detector at 260 nm wavelength. In port A of the mobile phase, 100% Potassium di-hydrogen phosphate buffer, pH 3.0, was kept, and in port B, 100% Acetonitrile was kept. Separation was achieved by using a Sunniest C18 column having dimensions 150 × 4.6 mm, 3 μm. 1.0 ml/min flow rate was set with column temperature 30 °C. Total run time was 40 min showed separation of all three components i.e. Brompheniramine Maleate (BPM) retention time (RT) − 23.64, Dextromethorphan HBr (DMP) RT – 25.22, Phenylephrine HCl (PPN) RT – 3.66 and BPM’s impurities such as Chlorpheniramine related compound B (Impurity A) RT – 22.81, Chlorpheniramine (Impurity B) RT – 11.06, and Pheniramine (Impurity C) RT – 14.96 with resolution ≥ 2.0. A linear relationship (r = 0.99) was revealed for all known analytes with a concentration range of LOQ to 150%. The recovery study specifies the accuracy of the method obtained in a range of 95%-105%. The repeatability determined that the method is precise enough within the acceptance limit of 80%-120%. Excellent linearity, accuracy, specificity, precision, robustness, LOD, LOQ and system applicability results are shown by the proposed approach.

Abstract licence: CC BY-NC-ND

Serotonin syndrome (SS) is a potentially life-threatening condition caused by excessive serotonergic activity in the central nervous system. It is commonly linked to combinations of serotonergic prescription drugs; however, over-the-counter or prescription cold medications containing dextromethorphan (DM) or first-generation antihistamines may also pose a risk. We report a case of a 52-year-old male on sertraline who developed SS after taking Bromfed DM, a cough syrup containing brompheniramine, pseudoephedrine, and DM. Three days after starting the medication, he experienced confusion, dilated pupils, myoclonic foot movements, and difficulty with speech. Symptoms improved following the discontinuation of both sertraline and Bromfed DM. This case underscores the importance of recognizing the serotonergic potential of common cold medications and the risk of SS even at therapeutic doses, particularly in patients on selective serotonin reuptake inhibitors (SSRIs). Prompt identification and cessation of the causative agents are critical to avoid complications.

Abstract licence: CC BY

The investigation of pharmaceuticals as emerging contaminants in marine biota has been insufficient. In this study, we examined the presence of 51 pharmaceuticals in edible oysters along the coasts of the East and South China Seas. Only nine pharmaceuticals were detected. The mean concentrations of all measured pharmaceuticals in oysters per site ranged from 0.804 to 15.1 ng g–1 of dry weight, with antihistamines being the most common. Brompheniramine and promethazine were identified in biota samples for the first time. Although no significant health risks to humans were identified through consumption of oysters, 100–1000 times higher health risks were observed for wildlife like water birds, seasnails, and starfishes. Specifically, sea snails that primarily feed on oysters were found to be at risk of exposure to ciprofloxacin, brompheniramine, and promethazine. These high risks could be attributed to the monotonous diet habits and relatively limited food sources of these organisms. Furthermore, taking chirality into consideration, chlorpheniramine in the oysters was enriched by the S-enantiomer, with a relative potency 1.1–1.3 times higher when chlorpheniramine was considered as a racemate. Overall, this study highlights the prevalence of antihistamines in seafood and underscores the importance of studying enantioselectivities of pharmaceuticals in health risk assessments.

Abstract licence: CC BY