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Galen Medical Journal 2018Design, formulation and physicochemical evaluation of dimenhydrinate 25 mg oral tablets that disintegrate in oral cavity in a proper time. This product is easy to use...
BACKGROUND
Design, formulation and physicochemical evaluation of dimenhydrinate 25 mg oral tablets that disintegrate in oral cavity in a proper time. This product is easy to use for babies, geriatrics and people who have difficulty in swallowing.
MATERIALS AND METHODS
31 formulations were designed in 3 categories via Design-Expert software version 7. Group 1 consist of super-disintegrating bases, group 2 consist of effervescent bases and group 3 consist of super-disintegrating and effervescent bases together. Proposed by DesignExpert software, the optimum formulations were selected in each category and the tablets were produced by direct compression method. Tablets evaluated by friability, thickness, hardness, weight variation, drug content, content uniformity, disintegration time, wetting time, dissolution and moisture uptake tests.
RESULTS
The angle of repose and compressibility index of formulations were in the range of 24.65-29.08 and 5.02-9.01 % respectively. Thickness, hardness, wetting time, friability and content uniformity of formulations were in the range of 3.36-3.84 mm, 33.25-38.03 N, 19-37 seconds, 0.31-0.42 % and 96.44-99.02 % respectively. Disintegration time of the groups 1, 2 and 3 were in the range of 16-70, 47-72 and 12-35 seconds respectively.
CONCLUSION
Mixture of powders and orally dispersible tablets passed all tests. The results showed that formulations containing both of super-disintegrants and effervescent bases had better disintegration time compare to other formulations.
PubMed: 34466419
DOI: 10.22086/gmj.v0i0.936 -
Clinical Drug Investigation Nov 2019Vertigo derived from peripheral vestibular disorders is quite frequently encountered in daily clinical practice and can be a severely disabling symptom associated with... (Comparative Study)
Comparative Study Randomized Controlled Trial
Efficacy and Safety of a Fixed Combination of Cinnarizine 20 mg and Dimenhydrinate 40 mg vs Betahistine Dihydrochloride 16 mg in Patients with Peripheral Vestibular Vertigo: A Prospective, Multinational, Multicenter, Double-Blind, Randomized, Non-inferiority Clinical Trial.
BACKGROUND AND OBJECTIVE
Vertigo derived from peripheral vestibular disorders is quite frequently encountered in daily clinical practice and can be a severely disabling symptom associated with substantial impairment of health-related quality of life for the affected patients. Betahistine, a structural analogue of histamine and presumably the most widely prescribed anti-vertigo drug worldwide, has previously been shown to be an effective and safe treatment for these patients. The objective of the present study was to evaluate whether the fixed combination of cinnarizine and dimenhydrinate (Arlevert) is non-inferior and thus a potentially useful alternative to betahistine dihydrochloride in the treatment of patients suffering from peripheral vestibular vertigo.
METHODS
In this prospective, multicenter, double-blind, randomized, non-inferiority clinical trial, outpatients from 8 ENT clinics in Austria, Bulgaria, the Czech Republic and Russia were randomly assigned to receive three times daily one tablet of either the fixed combination cinnarizine 20 mg/dimenhydrinate 40 mg or betahistine dihydrochloride 16 mg for 4 weeks. Primary endpoint was the reduction of the mean vertigo score (MVS), a validated 12-item composite score defined as the mean of 6 vertigo symptoms (dystasia and walking unsteadiness, staggering, rotary sensation, tendency to fall, lift sensation, blackout) and 6 trigger factors for vertigo (change of position, bowing, getting up, driving by car/train, head movements, eye movement), after 4 weeks of therapy, as judged by the patient on a 5-point visual analogue scale (VAS). The non-inferiority margin was set to 0.3. Secondary outcomes included the patient's and investigator's judgment of global efficacy, the patient's rating of impairment of daily activities, and safety/tolerability of the treatments.
RESULTS
Three hundred and six patients (mean age 53.5 years, approximately 60% female) were enrolled and randomized to the fixed combination cinnarizine/dimenhydrinate (n = 152) or betahistine (n = 154) groups; 297 patients completed the study and 294 (146 and 148, respectively) were valid for the per-protocol analysis, which was used for the non-inferiority analysis. Treatment with cinnarizine/dimenhydrinate led to a stronger reduction of the MVS [least squares mean (LSM)] after 4-week therapy (primary endpoint) in comparison to betahistine (0.395 vs 0.488; difference: - 0.093, 95% CI - 0.180; - 0.007, p = 0.035); since the upper limit of the two-sided 95% confidence interval was not only below the non-inferiority margin of 0.3, but also entirely below 0, superiority of the fixed combination could be demonstrated. The combination preparation was also more effective after 1 week of therapy and received more favorable patient's ratings on overall efficacy and impairment of daily activities. Both treatments were very well tolerated. Only 12 patients (3.92%) reported 13 non-serious adverse events; 2 cinnarizine/dimenhydrinate-treated patients discontinued the study prematurely due to adverse events as compared to 5 betahistine-treated patients.
CONCLUSION
The fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg was found to be not only non-inferior, but superior to betahistine 16 mg in the improvement of peripheral vestibular vertigo. Furthermore, taking into account a good and slightly favorable safety profile, the present study provides evidence that the fixed-combination preparation is a potent and even superior alternative to betahistine in the treatment of vertigo related to peripheral vestibular disorders.
STUDY REGISTRATION
EudraCT No. 2011-004025-27.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Betahistine; Cinnarizine; Dimenhydrinate; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Prospective Studies; Vertigo; Young Adult
PubMed: 31571128
DOI: 10.1007/s40261-019-00858-6 -
Veterinary Dermatology Apr 2019Histamine type-1 (H1) receptor antagonists such as diphenhydramine are frequently used for treatment of pruritus in dogs, yet therapeutic efficacy for allergic disorders... (Comparative Study)
Comparative Study
Diphenhydramine pharmacokinetics after oral and intravenous administration of diphenhydramine and oral administration of dimenhydrinate to healthy dogs, and pharmacodynamic effect on histamine-induced wheal formation: a pilot study.
BACKGROUND
Histamine type-1 (H1) receptor antagonists such as diphenhydramine are frequently used for treatment of pruritus in dogs, yet therapeutic efficacy for allergic disorders is reported to be highly variable. Dimenhydrinate is a salt of diphenhydramine and 8-chlorotheophylline, and has been reported to produce superior oral absorption of diphenhydramine.
HYPOTHESIS/OBJECTIVE
To determine the pharmacokinetic and pharmacodynamic properties of diphenhydramine in dogs after intravenous (1 mg/kg) and oral (5 mg/kg) administration, and when given orally as dimenhydrinate at a dose of 10 mg/kg (≈5 mg/kg diphenhydramine).
ANIMALS
Each drug was administered to six healthy, fasted mixed-breed dogs in a research facility, using a cross-over design.
METHODS AND MATERIALS
Blood samples were collected for pharmacokinetic analysis of diphenhydramine and chlorotheophylline at defined intervals. Pharmacodynamic response was measured by histamine-mediated cutaneous wheal formation.
RESULTS
There was great variability in the data and one dog was an extreme outlier. The mean systemic availabilities of diphenhydramine were 7.8% and 22.0% after oral administration of diphenhydramine and dimenhydrinate, respectively, whereas the mean maximum concentrations were 36 (± 20) and 124 (± 46) ng/mL. The terminal elimination half-lives of diphenhydramine and dimenhydrinate were 5.0 (± 7.1) and 11.6 (± 17.7) h, respectively. Plasma diphenhydramine concentrations did not correlate with the percentage reduction in histamine-induced wheal formation. Theophylline reached plasma concentrations considered to be therapeutic for dogs.
CONCLUSION
Oral absorption of diphenhydramine was approximately three times greater with a longer half-life when it was administered as the combination product dimenhydrinate.
Topics: Administration, Intravenous; Administration, Oral; Animals; Cross-Over Studies; Dimenhydrinate; Diphenhydramine; Dogs; Female; Half-Life; Histamine; Histamine Antagonists; Male; Pilot Projects; Theophylline; Urticaria
PubMed: 30779257
DOI: 10.1111/vde.12727 -
Anasthesiologie, Intensivmedizin,... Apr 2015Nausea and vomiting are frequent symptoms in emergency medicine and require a targeted drug intervention. Despite known disadvantages in terms of efficacy and side... (Review)
Review
Nausea and vomiting are frequent symptoms in emergency medicine and require a targeted drug intervention. Despite known disadvantages in terms of efficacy and side effects, metoclopramide is still often used in the emergency medical service to treat nausea and vomiting. Recent studies show that, especially in the therapy of opioid-triggered vomiting, metoclopramide is not significantly effective when compared to placebo. Dimenhydrinate seems to be an effective drug for various forms of nausea, but can often be relatively or absolutely contraindicated in emergency medicine due to its sedative effect. Based on a literature review, 5-HT3-antagonists appear to be a good alternative for the treatment of emesis in the emergency service. However, as for all antiemetics, the maximum dosage and potential side effects need to be paid attention to. In addition, neither of the 5-HT3-antagonists are approved for therapy of non-chemotherapy-induced vomiting or PONV. In conclusion, it may be considered to include 5-HT3-antagonists in addition to dimenhydrinate in the ambulance medical equipment. The routine use of a specific antiemetic is not recommended.
Topics: Antiemetics; Dimenhydrinate; Emergency Medical Services; Emergency Medicine; Humans; Metoclopramide; Postoperative Nausea and Vomiting; Serotonin 5-HT3 Receptor Antagonists
PubMed: 25919820
DOI: 10.1055/s-0041-100894 -
Aesthetic Plastic Surgery Feb 2018
Topics: Antiemetics; Dexamethasone; Dimenhydrinate; Double-Blind Method; Drug Therapy, Combination; Humans; Nausea; Ondansetron; Vomiting
PubMed: 29026948
DOI: 10.1007/s00266-017-0972-2 -
Wilderness & Environmental Medicine Jun 2022Acute altitude exposure is a common event in Latin America that can result in mild to severe altitude illness. Medical students from some Latin American countries...
INTRODUCTION
Acute altitude exposure is a common event in Latin America that can result in mild to severe altitude illness. Medical students from some Latin American countries receive little information on this topic. Our aim was to determine the knowledge and incidence of acute mountain sickness (AMS), as well as the methods used to prevent AMS among medical students attending the Pan-American Student Meeting in Cusco, Peru, a city at high altitude (3400 m).
METHODS
We conducted a cross-sectional study on medical students attending a conference. Participants completed a questionnaire on the day of registration that collected demographic data and investigated students' knowledge of AMS, its prophylaxis, and their personal experience of symptoms.
RESULTS
A total of 840 students attended the meeting. Two hundred eighty-eight returned surveys, 51 from high altitude locations. Respondent age was 23±3 y (mean±SD), and 72% were female. Thirty-two percent had basic knowledge about symptoms of AMS. Headache was recognized as a symptom by 79%. Knowledge of AMS prophylaxis was reported by 70%. Coca leaf products and dimenhydrinate were mentioned by 30 and 16%, respectively, whereas acetazolamide was recognized by only 10% of participants. AMS incidence was 42%. Prophylactic measures were adopted by 47% of the participants in our study. Thirty-six percent used dimenhydrinate and 27% used coca tea. Less than 1% used acetazolamide as recommended.
CONCLUSIONS
We found poor knowledge of AMS and effective prophylaxis among medical students from several South American countries traveling to 3400 m.
Topics: Acetazolamide; Acute Disease; Altitude Sickness; Cross-Sectional Studies; Dimenhydrinate; Female; Humans; Latin America; Male; Students, Medical
PubMed: 35361528
DOI: 10.1016/j.wem.2021.12.004 -
Medicine Sep 2022Airway neutrophilia has been associated with asthma severity and asthma exacerbations. This study attempted to identify biomarkers, pathogenesis, and therapeutic...
BACKGROUND
Airway neutrophilia has been associated with asthma severity and asthma exacerbations. This study attempted to identify biomarkers, pathogenesis, and therapeutic molecular targets for severe asthma in neutrophils using bioinformatics analysis.
METHODS
Fifteen healthy controls and 3 patients with neutrophilic severe asthma were screened from the Gene Expression Omnibus (GEO) database. Based on the analysis of differentially expressed genes (DEGs), functional and pathway enrichment analyses, gene set enrichment analysis, protein-protein interaction network construction, and analysis were performed. Moreover, small-molecule drug candidates have also been identified.
RESULTS
Three hundred and three upregulated and 59 downregulated genes were identified. Gene ontology function enrichment analyses were primarily related to inflammatory response, immune response, leukocyte migration, neutrophil chemotaxis, mitogen-activated protein kinase cascade, Jun N-terminal kinase cascade, I-kappaB kinase/nuclear factor-κB, and MyD88-dependent toll-like receptor signaling pathway. Pathway enrichment analyses and gene set enrichment analysis were mainly involved in cytokine-cytokine receptor interaction, the TNF signaling pathway, leukocyte transendothelial migration, and the NOD-like receptor signaling pathway. Furthermore, 1 important module and 10 hub genes (CXCL8, TLR2, CXCL1, ICAM1, CXCR4, FPR2, SELL, PTEN, TREM1, and LEP) were identified in the protein-protein interaction network. Moreover, indoprofen, mimosine, STOCK1N-35874, trapidil, iloprost, aminoglutethimide, ajmaline, levobunolol, ethionamide, cefaclor, dimenhydrinate, and bethanechol are potential drugs for the treatment of neutrophil-predominant severe asthma.
CONCLUSION
This study identified potential biomarkers, pathogenesis, and therapeutic molecular targets for neutrophil-predominant severe asthma.
Topics: Ajmaline; Aminoglutethimide; Asthma; Bethanechol; Biomarkers; Cefaclor; Computational Biology; Cytokines; Dimenhydrinate; Ethionamide; Gene Expression Profiling; Humans; Iloprost; Indoprofen; JNK Mitogen-Activated Protein Kinases; Levobunolol; Mimosine; Mitogen-Activated Protein Kinases; Myeloid Differentiation Factor 88; NF-kappa B; NLR Proteins; Neutrophils; Receptors, Cytokine; Toll-Like Receptor 2; Trapidil; Triggering Receptor Expressed on Myeloid Cells-1
PubMed: 36197221
DOI: 10.1097/MD.0000000000030661 -
Spectrochimica Acta. Part A, Molecular... Sep 2021Antiemetic drugs are used to control excessive vomiting and nausea and generally absorbed through gastrointestinal tract. In present study, the in-vitro binding...
Antiemetic drugs are used to control excessive vomiting and nausea and generally absorbed through gastrointestinal tract. In present study, the in-vitro binding interactions two of the antiemetic drugs (dimenhydrinate and ondansetron) between Trypsin (Tsn) secreted from pancreas to small intestine for protein digestion were investigated by fluorescence emission spectroscopy (FES), UV-VIS spectroscopy, synchronous fluorescence spectroscopy (SFS), FT-IR spectroscopy and molecular modeling methods. Also, the effect of these drugs on the catalytic activity of Tsn was determined. The fluorescence quenching experiments indicated that each drugs quenched the intrinsic fluorescence of Tsn with their increased concentrations. The results of SFS and UV-VIS spectra proved the interaction of dimenhydrinate and ondansetron with Tsn. FT-IR spectra showed that the secondary structure of enzyme was altered in the presence of the drugs. All these spectroscopy results were validated and explained by molecular docking studies. Both drugs have inhibition effect on the catalytic activity of Tsn and the IC values were determined as 2.6 × 10 M and 6.4 × 10 M for dimenhydrinate and ondansetron, respectively. Docking results revealed that the hydrogen bond interaction of dimenhydrinate with active-site residue Ser195 and ondansetron with active-site residues His57 and Ser195 hydrogen bonds might be cause the inhibition of enzyme activity. The results of this study can provide valuable information in the field of pharmacokinetics and pharmacodynamics.
Topics: Antiemetics; Binding Sites; Hydrogen Bonding; Molecular Docking Simulation; Protein Binding; Spectrometry, Fluorescence; Spectroscopy, Fourier Transform Infrared; Thermodynamics; Trypsin
PubMed: 33901946
DOI: 10.1016/j.saa.2021.119817 -
Pakistan Journal of Pharmaceutical... May 2018A simple, sensitive and rigorous method for estimation of dimenhydrinate in human plasma was searched and its validation was carried out. LLE (Liquid-Liquid extraction)...
A simple, sensitive and rigorous method for estimation of dimenhydrinate in human plasma was searched and its validation was carried out. LLE (Liquid-Liquid extraction) of analyte with mixture of Hexane and ethyl acetate (1:1 v/v) was carried out for the preparation of Plasma Samples, Chromatographic elution of dimenhydrinate was conducted in human plasma and mobile phase with C-18 bonda Pack column (10μm; 250 × 4.6), using a mobile phase consisting a solution of ammonium bicarbonate in water and methanol at a flow rate of 0.5ml/minute with UV detection at 229 nm. The resolution of dimenhydrinate was well performed from plasma components. This method was validated and exhibited linearity with concentration range of 6 to 380ng/ml of dimenhydrinate in plasma. The Intra day precision was 89.2 to 96.89% and Inter day precision was 88.6% to 93.26%, the average recovery of dimenhydrinate was 97.02%. The efficacy of extraction was proved by above mentioned results. 2ng/ml and 6ng/ml, were appraised as the LOD and LOQ of dimenhydrinate, stability studies disclosed that dimenhydrinate exhibited stability in Plasma after Freeze & thaw cycles and upon -20°C storage, the method was developed well.
Topics: Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Dimenhydrinate; Drug Stability; Humans; Limit of Detection; Liquid-Liquid Extraction; Reference Standards; Spectrophotometry, Ultraviolet; Temperature
PubMed: 29731433
DOI: No ID Found -
Acute Inhibition of the Human Kv1.5 Channel by H Receptor Antagonist Dimenhydrinate: Mode of Action.Biological & Pharmaceutical Bulletin 2023Dimenhydrinate, an H receptor antagonist, is generally used for the prevention and treatment of nausea and vomiting. However, cardiac arrhythmias have been reported to...
Dimenhydrinate, an H receptor antagonist, is generally used for the prevention and treatment of nausea and vomiting. However, cardiac arrhythmias have been reported to be associated with the overdose of histamine H receptor antagonists, indicating the probable effect of antihistamines on ion channels. By using a two-microelectrode voltage clamp, we have herein studied the electrophysiological effects of dimenhydrinate on the human Kv1.5 channel in the Xenopus oocyte expression system. Dimenhydrinate acutely and reversibly suppressed the amplitudes of the peak and the steady-state current, within 6 min. The inhibitory effect of dimenhydrinate on the peak and the steady-state Kv1.5 currents increased progressively from -10 to +50 mV. At each test voltage, the drug suppressed both the peak and the steady-state currents to a similar extent. When the oocytes were stimulated at the rates of 5- and 30-s intervals, dimenhydrinate-induced a use-dependent blockade of the human Kv1.5 channel. Dimenhydrinate expedited the timecourse of the Kv1.5 channel activation more effectively than the timecourse of its inactivation. However, the activation and inactivation curves of the channel were not altered by the H receptor antagonist. In conclusion, we found that dimenhydrinate inhibits the human Kv1.5 channel by changing the channel's activation mode, thereby possibly increasing the possibility of triggering cardiac arrhythmias and affecting atrial fibrillation.
Topics: Humans; Dimenhydrinate; Electrophysiological Phenomena; Histamine H1 Antagonists; Oocytes; Potassium Channel Blockers
PubMed: 37779040
DOI: 10.1248/bpb.b23-00170