This study introduces a twin enrichment strategy based on dual-template molecularly imprinted polymer-assisted solid-phase microextraction coupled with dispersive liquid-liquid microextraction (MISPE-DLLME) for the simultaneous extraction and determination of favipiravir and remdesivir in biological matrices (blood and urine), followed by high-performance liquid chromatography with ultraviolet detection (HPLC-UV) analysis. The dual-template molecularly imprinted polymer (DT-MIP) was synthesized via precipitation polymerization and comprehensively characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), field-emission scanning electron microscopy (FESEM), Brunauer-Emmett-Teller (BET) surface area analysis, simultaneous thermal analysis (STA), and X-ray diffraction (XRD). Under optimized conditions, including pH 2.00 ± 0.1, 10.0 mg of MIP, 200 ± 5 μL of 1-dodecanol, 500 ± 10 μL of methanol, and an extraction time of 10.0 ± 0.5 min, the method afforded high recoveries of 103-110% with relative standard deviations (RSDs) below 5% (n = 3). The method showed excellent sensitivity, with limits of detection of 1.0 ng/mL for favipiravir and 0.40 ng/mL for remdesivir and limits of quantification of 3.3 ng/mL and 1.3 ng/mL, respectively. Selectivity was evaluated against ten structurally related drugs (ibuprofen, gemfibrozil, paracetamol, diazepam, clobazam, methocarbamol, theophylline, naproxen, dimenhydrinate, and cinnarizine) at various concentration ratios, and the DT-MIP displayed superior recognition performance compared with the corresponding non-imprinted polymer (NIP). Analysis of clinical samples yielded acceptable recoveries and precision, confirming the reliability of the proposed method and its potential applicability in therapeutic drug monitoring of COVID-19 antivirals.

Background: Nausea and vomiting in pregnancy affects up to 80% of pregnant women and may progress to hyperemesis gravidarum, leading to maternal morbidity and adverse pregnancy outcomes. Despite numerous pharmacological and non-pharmacological options, the comparative efficacy and safety of these interventions remain unclear. Methods: We conducted a systematic review and network meta-analysis of randomized controlled trials assessing pharmacological and non-pharmacological interventions for nausea and vomiting in pregnancy. The databases searched included CENTRAL, PubMed, and EMBASE (up to 28 May 2024). Eligible trials compared interventions with a placebo in pregnant women with nausea and vomiting in pregnancy. The primary outcomes were symptom severity, assessed using validated tools. Safety outcomes included adverse effects. Data were pooled using frequentist pairwise and network meta-analyses. The risk of bias was assessed using the RoB2 tool, and the certainty of evidence was evaluated using the CINeMA framework. Results: Of 9844 records screened, 24 randomized controlled trials (3017 participants) met the inclusion criteria, encompassing 16 intervention categories. Network analysis ranked quince, vitamin B6 with pomegranate and mint, acupressure P6, dimenhydrinate, and acupuncture combined with doxylamine-pyridoxine as the most effective interventions for reducing symptoms of nausea and vomiting in pregnancy, with considerable uncertainty and low-to-moderate quality of evidence. Reporting of adverse events was limited. Risk of bias was low to moderate. Discussion: Most interventions demonstrated significant benefit over a placebo. However, high heterogeneity and sparse reporting of adverse effects warrant caution when translating these results into clinical practice. Conclusions: This study indicates that both pharmacological (vitamin B6, metoclopramide, dimenhydrinate) and non-pharmacological (ginger, quince, acupressure, acupuncture) interventions might be effective in reducing symptoms of nausea and vomiting in pregnancy.

Kounis syndrome is an under-recognized condition characterized by the simultaneous occurrence of acute coronary syndrome and hypersensitivity reactions. While opioids are known triggers, tramadol-induced Kounis syndrome is extremely rare. A 49-year-old woman with a history of allergy to dimenhydrinate and chronic low back pain developed anaphylactic shock 4 min after receiving 50 mg of subcutaneous tramadol. She developed with dyspnea, glottic edema, muscle rigidity, chest pain, and hypotension. After stabilization with epinephrine, corticosteroids, antihistamines, fluids, and vasopressors, elevated cardiac biomarkers were detected. Electrocardiograms and echocardiography were normal. Coronary CT and invasive angiography revealed no obstructive coronary artery disease. A diagnosis of Kounis syndrome was established. This case highlights the importance of considering Kounis syndrome in patients presenting with anaphylaxis and chest pain, even in the absence of ECG changes. Early hemodynamic stabilization followed by cardiac evaluation is essential for timely diagnosis and management.

The aim of this study was to optimize and evaluate dimenhydrinate fast dispersible tablets (50 mg) by utilizing cost effective direct compression method. A total of nine formulations (F1-F9) were designed and developed by central composite rotatable design using design expert® software (version 11.0, Stat-Ease Inc.,) to study the impact of avicel PH102 (15-55%) and sodium starch glycolate (2-8%) on responses, i.e., hardness (R1), disintegration time (R2) and % drug release (R3). Powder blends of all formulations showed good flow behavior. Post compressional studies were conducted to assess the quality attributes of the compressed formulations. Formulation F2 was found to be optimized with good mechanical strength, i.e., hardness 4.2 kg, friability 0.77%, disintegration time 19 secs and % drug release 100.01% at 15 minutes. Compressional behavior of optimized formulation was determined with the help of Heckle plot. The PY (yield value) and the tensile strength of the optimized formulation (F2) were found to be 66.66 MN/m2 and 1.093 ± 1.66 to 1.642 ± 1.76 MN/m2 respectively. Differential scanning calorimetric and scanning electron microscopy analysis were performed to explore compatibility between ingredients and morphological features. All formulations followed weibull model in four different dissolution media. All the formulations were found to be stable at accelerated conditions. The in-silico GastroPlus™ PBPK modeling was also carried out to determine the pharmacokinetic parameters of the optimized formulation (F2) as an alternative to in vivo dimenhydrinate studies. Simulated PK values of F2 were found to be 143.16 ng/ml (Cmax), 2 h (Tmax), 2533.8 ng-h/ml (AUC 0-inf) and 1477.9 ng-h/ml (AUC 0-t). Results indicated that the fold error value was > 2 which indicated that experimental values are comparable with the predicted values. This type of study will be helpful for pharmaceutical manufacturers to produce patient compliance, low-cost tablet dosage form.

Pharmaceutical and personal care products (PPCPs), as ubiquitous emerging contaminants, present undercharacterized neuropsychiatric hazards through environmental exposure. This investigation employs convergent multi-omics strategies - integrating toxicogenomic discovery, disease-associated genomic mapping, and transcriptomic profiling - to elucidate mechanistic linkages between PPCPs bioactivity and depressive pathogenesis. Through systematic analysis of Nanjing's aquatic chemical burden (prioritizing dimenhydrinate, ibuprofen, padimate-O, caffeine, and roxithromycin), we identified 3073 conserved molecular targets bridging PPCPs toxicity and depression etiology via Comparative Toxicogenomics Database and GeneCards interrogation. Functional ontology revealed dysregulated pathways encompassing lipidomic remodeling, IL-17-mediated neuroinflammation, and synaptic transmission deficits. Ensembled machine learning algorithms (Lasso regression, XGBoost, random forest) converged on seven high-fidelity candidate biomarkers (HSPA8, CBX1, CD59, CHAF1A, CUX1, ID2, RPL3) demonstrating stress-adaptive, chromatin regulatory, and immunomodulatory functions. Molecular docking predicted strong binding affinities between PPCPs and depression-related proteins, notably dimenhydrinate with CHAF1A (- 6.1 kcal/mol) and HSPA8 (- 6.1 kcal/mol), suggesting multi-target modulation. This work proposes a computational framework to map molecular interactions between specific PPCPs and depression-associated pathways. Candidate targets highlight testable hypotheses for future experimental validation. These findings suggest selected PPCPs with neuroactive properties may warrant further investigation as environmental modifiers of depression risk.

Vertigo is a frequent reason for medical consultation and may result from a wide range of aetiologies. Betahistine and the fixed low-dose combination of cinnarizine 20 mg and dimenhydrinate 40 mg are commonly used therapeutic options, each with distinct antivertigo profiles. This systematic review, conducted in accordance with the PRISMA guidelines, aims to compare the efficacy and safety of these two treatments in patients with vertigo of various origins. A comprehensive search was conducted in PubMed, Cochrane Library, Google Scholar, and ClinicalTrials.gov, with no restrictions on language or publication date. Eligible studies included clinical trials and meta-analyses comparing the fixed low-dose combination (20 mg/40 mg) versus betahistine (12 or 16 mg), assessing efficacy through the Mean Vertigo Score (MVS) and safety based on the incidence of adverse events (AEs). The RoB 2 and ROBIS tools were used to evaluate the risk of bias. A total of nine studies were identified (six clinical trials and three meta-analyses). In five of the six clinical trials, the fixed low-dose combination significantly reduced MVS compared with betahistine at weeks 1 and/or 4 (p < .05); these findings were corroborated by the three meta-analyses. Regarding safety, both treatments were well tolerated, with no serious AEs reported and a generally lower incidence observed in the fixed low-dose combination group. Overall, the fixed low-dose combination demonstrated superior clinical efficacy from the first week of treatment, along with a more favourable tolerability and safety profile. These results support its preferential use in the management of acute vestibular syndrome.

Several studies have described the sedative effects of dimenhydrinate (DMH), although others report a stimulant effect on psychomotor functions. Because the first generation of antihistamines was shown to seriously impair cognitive psychomotor and driving performance in healthy volunteers, the aim of our research was to determine the effect of DMH by testing physical activity and cognitive and cardiovascular functions using an animal model to identify a possible stimulatory effect. The study protocol consisted of two phases. The first was designed to analyze the stimulating motor effect of DMH. Four study groups were formed: (1) vehicle (Veh), (2) modafinil (MOD), (3) DMH at 50 mg/kg (DMH-50), and (4) DMH at 200 mg/kg (DMH-200). Motor coordination and balance, physical activity, hemodynamics, and nitrous oxide (NO) quantification were performed. In the second phase, we sought to discriminate the compound in DMH that generates the stimulating effect. In this case, the study groups were (1) Veh, (2) MOD, (3) DMH, (4) diphenhydramine (DPH), (5) 8-chlorotheophylline (8-Cl-T), and (6) theophylline (TEO). In this phase, we quantified glucose and insulin levels, behavior, physical activity, blood pressure, and vascular reactivity to phenylephrine and acetylcholine. Findings showed that DMH might improve a motor and physical stimulating effect but also increased NO levels in the lungs. DPH promoted a compulsive-like behavior that diminished with 8-Cl-T. Regarding cardiovascular effects, DMH decreased vascular reactivity to phenylephrine and acetylcholine. Finally, in the DMH formulation, 8-Cl-T was identified as the compound responsible for increasing blood pressure and heart rate.