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BMJ Case Reports 2009The present report highlights the possible adverse effects of doxylamine, a common over the counter sleep aid. Doxylamine is an antihistamine that at toxic doses can...
The present report highlights the possible adverse effects of doxylamine, a common over the counter sleep aid. Doxylamine is an antihistamine that at toxic doses can cause anticholinergic effects, including seizures, rhabdomyolysis and death. The following case describes a patient with doxylamine toxicity who presented with seizure and confusion. Our patient was managed symptomatically, and remained otherwise stable throughout his hospitalisation. This case is atypical in terms of a delayed rhabdomyolysis and a false positive urine drug screen test for methadone. There is evidence that doxylamine at toxic levels can lead to false positives for methadone and phencyclidine testing using immunoassay-based urine drug screen kits. Urine drug screen testing on patients who are hospitalised is typically performed using immunoassays. However, in certain cases confirmatory secondary testing may be required. Doxylamine is prone to abuse and knowledge of the clinical presentation of its toxicity and the management of acute overdose can be life-saving.
PubMed: 21686586
DOI: 10.1136/bcr.09.2008.0879 -
Bioengineered Dec 2021Recent findings have identified microbiota as crucial participants in many disease conditions, including cancers. Competing endogenous RNA (ceRNA) is regarded as a...
Recent findings have identified microbiota as crucial participants in many disease conditions, including cancers. Competing endogenous RNA (ceRNA) is regarded as a candidate mechanism involving relevant biological processes. We therefore constructed a ceRNA network using the TCGA and GEO database, to determine the potential mechanisms of microbiota-mediated colorectal carcinogenesis and progression. We found a total of 75 lncRNAs, 8 miRNAs, and 9 mRNAs in the probiotics-mediated ceRNA network and a total of 49 lncRNAs, 4 miRNAs, and 3 mRNA in the pathobiont-mediated ceRNA network, which could induce the microbiota-mediated carcinogenesis and progression. The GO and KEGG analysis indicated that the ceRNA network is mainly enriched in the metabolic process, and two unique pathways (the p53 signaling pathway and microRNA in cancer), respectively. A four-gene signature (FRMD6-AS2, DIRC3, LIFR-AS1, and MRPL23-AS1) was suggested as an independent prognostic factor. Four lncRNAs (LINC00355, KCNQ1OT1, LINC00491, and HOTAIR) were associated with poor survival. Three small molecule candidate anticancer drugs (Pentoxyverine, Rimexolone, and Doxylamine) were identified. A four-gene signature (FAM129A, BCL2, PMAIP1, and RPS6) is significantly correlated with immune infiltration level. This study provides a promising biomarker reservoir to explore the mechanism by which microbiota regulate the ceRNA network involving the immune response, and further participate in colorectal carcinogenesis and progression.
Topics: Antineoplastic Agents; Colorectal Neoplasms; Computational Biology; Gastrointestinal Microbiome; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Prognosis; Protein Interaction Maps; RNA, Messenger; RNA, Untranslated
PubMed: 34227920
DOI: 10.1080/21655979.2021.1940614 -
American Family Physician Mar 2015Nausea and vomiting are mediated primarily by three neurotransmitter pathways: visceral stimulation releases dopamine and serotonin; vestibular and central nervous...
Nausea and vomiting are mediated primarily by three neurotransmitter pathways: visceral stimulation releases dopamine and serotonin; vestibular and central nervous system activation release histamine and acetylcholine; and chemoreceptor trigger zone activation releases dopamine and serotonin. Clinicians can improve the effectiveness and cost-effectiveness of treatments by targeting the appropriate pathways. Antihistamines and anticholinergics are most effective in patients with vestibular-mediated nausea secondary to vertigo. Serotonin antagonists block serotonin in the intestines and chemoreceptor trigger zone, and are most effective for treating gastroenteritis. Dopamine antagonists block dopamine in the intestines and chemoreceptor trigger zone; indications for these agents are similar to those for serotonin antagonists. For treatment of mild pregnancy-induced nausea, pyridoxine with or without doxylamine is recommended, and ginger may also be effective. In patients with migraine headache-associated nausea, metoclopramide improves response to oral anti-migraine agents. Ondansetron reduces nausea and vomiting in children with acute gastroenteritis and in women with hyperemesis gravidarum.
Topics: Antiemetics; Clinical Decision-Making; Female; Gastritis; Humans; Hyperemesis Gravidarum; Migraine Disorders; Nausea; Pregnancy; Vertigo; Vestibular Diseases; Vomiting
PubMed: 25822385
DOI: No ID Found -
Drugs in R&D Dec 2012Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. The data available on the... (Randomized Controlled Trial)
Randomized Controlled Trial
Food effects on the pharmacokinetics of doxylamine hydrogen succinate 25 mg film-coated tablets: a single-dose, randomized, two-period crossover study in healthy volunteers.
BACKGROUND
Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. The data available on the pharmacokinetic profile of doxylamine in humans are limited, notwithstanding that this drug has been marketed in European countries for more than 50 years. In fact, no data on the effect of food on the pharmacokinetic parameters of doxylamine are available.
OBJECTIVE
The objective of this study was to evaluate the pharmacokinetic parameters of doxylamine following a single oral dose of doxylamine hydrogen succinate 25 mg in healthy human subjects under fed and fasting conditions.
STUDY DESIGN
This was a single-center, randomized, single-dose, laboratory-blinded, two-period, two-sequence, crossover study.
SETTING
The study was conducted in a phase I clinical unit.
SUBJECTS AND METHODS
A single oral dose of doxylamine hydrogen succinate 25 mg (equivalent to 17.4 mg of doxylamine base) was administered to healthy volunteers under either fed conditions (high-fat, high-calorie food intake) or fasting conditions in each study period. The drug administrations were separated by a wash-out period of seven calendar days. Plasma samples were collected for up to 60 hours postdose, and plasma doxylamine concentrations were determined by a high-performance liquid chromatography method with tandem mass spectrometry detection. Pharmacokinetic parameters were calculated using noncompartmental analysis. Safety was evaluated through assessment of adverse events, standard laboratory evaluations, vital signs, and 12-lead electrocardiography.
RESULTS
In total, 24 healthy subjects (12 male and 12 female) were included in the study. Doxylamine succinate 25 mg tablets exhibited similar oral bioavailability of doxylamine in the fasting state (mean maximum plasma drug concentration [C(max)] 118.21 ng/mL, coefficient of variation [CV] 19.2%; mean area under the plasma concentration time curve from time zero to time t [AUC(t)] 1746.97 ng · h/mL, CV 31.6%) and in the fed state (mean C(max) 120.99 ng/mL, CV 15.0%; mean AUC(t) 1712.20 ng · h/mL, CV 26.7%). No statistically significant between-treatment differences were observed for any of the pharmacokinetic parameters under study. The fed : fasting ratios of the geometric least squares means with corresponding 90% confidence intervals for C(max) and AUC(t) were within the range of 80-125%.
CONCLUSION
High-fat, high-calorie food intake does not affect the kinetics of doxylamine in healthy subjects. The drug was safe and well tolerated by the subjects in this study.
Topics: Administration, Oral; Adult; Area Under Curve; Biological Availability; Cross-Over Studies; Doxylamine; Fasting; Female; Food-Drug Interactions; Half-Life; Humans; Male; Middle Aged; Tablets; Tablets, Enteric-Coated; Young Adult
PubMed: 23230999
DOI: 10.2165/11641640-000000000-00000 -
Canadian Family Physician Medecin de... Jan 2017
Topics: Canada; Doxylamine; Female; Guideline Adherence; Humans; Hyperemesis Gravidarum; Physicians, Family; Practice Guidelines as Topic; Pregnancy; Pyridoxine; Societies, Medical
PubMed: 28115431
DOI: No ID Found -
European Review For Medical and... Dec 2022
Reply Letter - to Urso et al "Comment on: Comparative dissolution profiles of two anti-emetic delayed release dosage forms of doxylamine and pyridoxine: Xonvea® tablets vs. Cariban® capsules".
Topics: Doxylamine; Pyridoxine; Antiemetics; Solubility; Ursodeoxycholic Acid; Tablets; Capsules; Gastrointestinal Agents; Delayed-Action Preparations
PubMed: 36524482
DOI: 10.26355/eurrev_202212_30533 -
BMC Chemistry Mar 2023A sequential spectrophotometric resolution technique (SSRT) was developed in this study without the use of systematic separation procedures to determine drug of a...
The simultaneous measurement of quaternary mixture in over-the-counter cold medications using sequential spectrophotometric resolution approach enhanced with in-lab sample enrichment.
A sequential spectrophotometric resolution technique (SSRT) was developed in this study without the use of systematic separation procedures to determine drug of a quaternary combination; caffeine (CAF), pseudoephedrine (PSE), doxylamine succinate (DOX), and paracetamol (PAR). Their presence in a tablet with a gap ratio of 3:3:1:150, respectively, and their overlapping spectra with low absorptivities make their resolution and determination impossible without prior separation. successive ratio subtraction technique (SRST) and constant multiplication method were used to solve these problems. Furthermore, an in-lab sample enrichment technique was applied to increase minor components concentration and consequently their absorbanses (CAF, PSE, and DOX). The D absorption spectra were generated by successive ratios followed by subtraction and multiplication of the constants. The maximum absorbances of the drugs tested, namely (CAF, PSE, DOX and PAR) were measured at wavelengths of 272.0, 257.0, 260.0, and 248.0 nm, respectively. The limits of detection (LOD) and limits of quantification (LOQ) were 0.021, 0.124, 0.186, 0.137 and 0.070, 0.414, 0.621, 0.456 (µg/mL), respectively. The linearitiy ranges (µg/mL) were 1.0-22.0, 1.0-24.0, 10.0-90.0 and 1.0-15.0 for CAF, PSE, DOX, and PAR, respectively. The International Conference on Harmonization (ICH) guidelines were applied for method validation, and the results obtained were within the limited parameters. The finding results were compared to official and/or published analytical methods to determine the procedure's reliability. It was noted that there was no actual difference in accuracy and precision between both meyhods. The proposed technique is sensitive, selective and economic;so it can be applied to the simultaneous analysis of these drugs in their commercial tablets and/or in quality-control laboratories.
PubMed: 36949535
DOI: 10.1186/s13065-023-00931-4 -
European Review For Medical and... Nov 2022
Topics: Doxylamine; Pyridoxine; Antiemetics; Solubility; Gastrointestinal Agents; Capsules; Tablets
PubMed: 36459003
DOI: 10.26355/eurrev_202211_30351 -
JAMA Otolaryngology-- Head & Neck... Sep 2020Sinonasal remedies are the most frequently purchased category of over-the-counter (OTC) drugs in the United States. A variety of options for relief are available under...
IMPORTANCE
Sinonasal remedies are the most frequently purchased category of over-the-counter (OTC) drugs in the United States. A variety of options for relief are available under proprietary names, although the actual number of available options may not be readily appreciated by the consumer or the clinician.
OBJECTIVE
To determine the prevalence of specific ingredients in OTC sinonasal products.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study took physical inventory of brand-name and generic OTC drugs marketed as sinus, cold, allergy, or nasal remedies. Retail pharmacies in New Orleans, Louisiana, commercial websites, and the Drugs, Herbs and Supplements section of MedlinePlus and drugs.com were searched. Data were collected and analyzed from July 1 to 31, 2018.
MAIN OUTCOMES AND MEASURES
Frequency of active ingredients in OTC formulations.
RESULTS
Five pharmacies were visited to identify 18 brands, for which the commercial websites were then searched. The 14 most common brands represented 211 unique products. Only 8 unique nonanalgesic ingredients were identified among these products, with many products sold under the same brand name and with the same active ingredient. Phenylephrine hydrochloride, dextromethorphan hydrobromide, pseudoephedrine hydrochloride, guaifenesin, chlorpheniramine maleate, brompheniramine maleate, diphenhydramine hydrochloride, and doxylamine succinate were the common active ingredients, with all available OTC sinonasal remedies consisting of 1 or more of these ingredients. The frequency of occurrence of each ingredient ranged from 10 to 261 different products. Combinations of 2, 3, or 4 active ingredients occurred frequently in OTC sinonasal products.
CONCLUSIONS AND RELEVANCE
These findings suggest that proliferation of brand extension products under a common name is pervasive. Clinicians should be aware of the large array of redundant OTC formulations and lack of specificity when discussing brand-name sinonasal remedies with their patients.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cross-Sectional Studies; Drug Combinations; Histamine Antagonists; Humans; Nonprescription Drugs; Respiratory System Agents; United States
PubMed: 32672802
DOI: 10.1001/jamaoto.2020.1836 -
Acta Pharmaceutica (Zagreb, Croatia) Mar 2018The prediction power of partial least squares (PLS) and multivariate curve resolution-alternating least squares (MCR-ALS) methods have been studied for simultaneous...
The prediction power of partial least squares (PLS) and multivariate curve resolution-alternating least squares (MCR-ALS) methods have been studied for simultaneous quantitative analysis of the binary drug combination - doxylamine succinate and pyridoxine hydrochloride. Analysis of first-order UV overlapped spectra was performed using different PLS models - classical PLS1 and PLS2 as well as partial robust M-regression (PRM). These linear models were compared to MCR-ALS with equality and correlation constraints (MCR-ALS-CC). All techniques operated within the full spectral region and extracted maximum information for the drugs analysed. The developed chemometric methods were validated on external sample sets and were applied to the analyses of pharmaceutical formulations. The obtained statistical parameters were satisfactory for calibration and validation sets. All developed methods can be successfully applied for simultaneous spectrophotometric determination of doxylamine and pyridoxine both in laboratory-prepared mixtures and commercial dosage forms.
Topics: Calibration; Doxylamine; Drug Compounding; Least-Squares Analysis; Multivariate Analysis; Pyridoxine; Spectrophotometry
PubMed: 29453910
DOI: 10.2478/acph-2018-0008