Granisetron is a selective 5-HT3 receptor antagonist that is used therapeutically for the prevention of vomiting and nausea associated with emetogenic cancer chemotherapy. Although this drug is commercially available for intravenous and oral dosage, there is a need for intranasal delivery formulations in specific patient populations in which the use of these dosage forms may be unfeasible and/or inconvenient. A rapid and specific high-performance liquid chromatography method with mass spectrometric detection(LC-MS) was developed and validated for the analysis of granisetron in plasma after nasal administration in rats. This method has been validated for concentrations ranging from 5 to 1000 ng/ml with simple treatment. This technique has high level reproducibility, accuracy, and sensitivity. The method described was found to be suitable for the analysis of all samples collected during preclinical pharmacokinetic investigations of granisetron in rats after nasal administration. This study was aimed to investigate the feasibility of nasal delivery of granisetron for the elimination of vomiting. The effects of osmolarity, dosage volume at the same dose and applied dose on the nasal absorption of granisetron in rats were observed. No significant difference in the effect of osmolarity and dosage volume at the same dose was observed. As the applied dose of granisetron in nasal formulation increased, the absorption increased linearly. Based on these results it appears that only the applied dose(drug mass) determines the nasal absorption of granisetron. The bioavailability of granisetron on nasal administration of 4 mg/kg appeared to be comparable to that of intravenous administration of the same dose. These results suggest that granisetron can be efficiently delivered nasally and the development of nasal formulation will be feasible.
In recent years intranasal administration of drugs has received great attention as a convenient and efficent method of drug delivery because of its potential to improve the systemic effect of substances with a poor oral bioavailability. In addition to offering advantages such as rapid absorption, fast onset of action and avoiding the first -pass effect, it provides for delivery of drugs from very lipophilic drugs such as steroids to polar and hydrophilic drugs such as peptides and proteins. However, little is still known about the nature of various barriers existing in the nasal mucosae as well as mechanism by which these molecules are absorbed. This review article therefore intends to discuss nasal physiology, experimental methods and evaluation of absorption from the nasal cavity, factors influencing nasal absorption, mechanism of nasal absorption, approaches to improve the residence time and to obtain the sustained-release effect of intranasally administered drugs, promoters and mechanism for the enhancement of nasal absorption, Several examples for intranasal delivery of various systemically effective drugs will be reviewed and illustrated. Drug metabolism in the nasal mucosae and problems associated with intranasal administration of drugs will be also discussed.
Nasal absorption of procyclidine, a synthetic anticholinergic compound, was investigated in Wistar rats and Beagle dogs. The dosing solution was prepared by dissolving$^{14}C$-procyclidme in 50% ethanolic saline. The dosing solution was administered intravenously and intranasally to rats at a dose of 0.6 mg/kg (i.e., $60{\mu}$l/kg in the form of a 1% w/v solution), and intravenously, orally and intranasally to doss at a dose of 0.3 mg/kg(i.e., $6{mu}$l/kg in the form of a 5% w/v solution). Blood samples were taken from an artery of the animals through the catheter for periods of 1200 (for rats) and 1440 min (for dogs), and the radioactivity in the samples was determined by liquid scintillation counting. The nasal bioavailability of Procyclidine in rats and dogs, based on the radioactivity was calculated to be 81.1 and 98.6% respectively. In both rats and dogs, the plasma profiles of procyclidine following nasal administration were very close to those following intravenous administration, leading to nearly superimposable profiles between the two protocols. In dogs, nasal administration resulted in significantly higher plasma concentrations during the first 30 min period compared to oral administration, suggesting the superiority of the nasal route over the oral route in terms of a prompt expression of the pharmacological effect of the drug. The results obtained in this study indicate that procyclidine is rapidly and nearly completely absorbed via the nasal route. In conclusion, nasal administration represents a viable alternative to intravenous administration in the case of procyclidine.
Background: Prophylactic antibiotic administration after surgery for a nasal bone fracture is performed due to concerns about infection-related complications, such as, toxic shock syndrome. To evaluate the validity and efficacy of antibiotic use, we compared the results obtained and the bacterial profiles of nasal packing materials in patients that underwent closed reduction for a nasal bone fracture with or without prophylactic antibiotic administration. Methods: Thirty consecutive patients with a nasal bone fracture, but without an open wound, that underwent closed reduction during March to August 2017 were included in the present study. Fifteen of these 30 patients were randomly assigned to a control group, members of were administered postoperative intravenous antibiotics once at the day of surgery and then oral antibiotics for 4 days. The other 15 patients were assigned to an experimental group and not administered any antibiotic postoperatively. Antibiotic ointment was not applied to nasal packing in either group. Nasal packing was removed on postoperative day 4 in all cases. Removed nasal gauze packings were culture tested and strains identified in the two groups were compared. Results: Bacterial strain types cultured from packings were similar in the experimental and control groups and no patient showed signs of clinically significant infection. Conclusion: The findings of this study suggest postoperative prophylactic antibiotic use is not clinically required after closed reduction of a nasal bone fracture. Furthermore, the non-use of postoperative antibiotics is biologically beneficial, as it reduces the occurrence of resistant strains and medical costs, and is more convenient for patients.
This study was designed to analyze normal nasal respiratory resistance in prepubertal children. The subjects consisted of 30 prepubertal children (male: 15, female: 15). The mean age was 11.4 years in male children and 11.5 years in female children. The results were as follows: I. The normal nasal respiratory patency was lower than the normal values from RION corp. 2. The normal nasal respiratory airflow rates showed no sexual differences. And there were no differences between inspiration and expiration. 3. Before and after use of nasal decongestants, there were no significant differences of normal nasal respiratory airflow rates and after the administration of nasal decongestants, nasal respiratory patency manifested lower variability. 4. The normal nasal respiratory resistance without nasal decongestants at 150 Pascal in inspiration was $0.30Pa/cm^3/sec({\pm}0.07)$ and peak nasal inspiratory airflow rate was $1016.83cm^3/sec({\pm}223.89)$. 5. The normal nasal respiratory resistance with nasal decongestant at 150 Pascal in inspiration was $0.25Pa/cm^3/sec({\pm}0.05)$ and peak nasal inspiratory airflow rate was $1148.33cm^3/sec({\pm}234.29)$.
Park, Gee-Bae;Seo, Bo-Youn;Ann, Hong-Jik;Rho, Hyun-Goo;Onn, Yun-Sung;Lee, Kwang-Pyo
Journal of Pharmaceutical Investigation
/
v.24
no.2
/
pp.95-104
/
1994
Inclusion complexes of ketoconazole(KT) with ${\alpha}^_$, ${\beta}^_$cyclodextrin(CD) and $dimethy1-{\beta}-cyclodextrin$ (CD) and $dimethy1-{\beta}-cyclodextrin(DM{\beta}CD)$ as nasal absorption enhancer were prepared in 1: 2 molar ratios by freeze-drying and solvent evaporation methods. In order to compare with the intrinsic absorptivity of KT in the jejunum(J) and the nasal cavity(N), the in situ simultaneous perfusion method was employed. The in situ recirculation study revealed that KT-CD inclusion complexes with the greater stability constant and the faster dissolution rate proportionally increased the absorption of KT in the J and N of rats. The rank order of apparent KT permeability$(P_{app}\;:\;cm/sec\;{\time}\;1O^{-5}{\pm}S.E.)$, corrected by surface area of absorption, was $5.10{\pm}0.3(N,\; KT-DM{\beta}CD)$ )> $4.13{\pm}0.4(N,\;KT-{\beta}-CD)$ )> $3.52{\pm}0.2(N,\;KT-{\alpha}-CD)$ )> $2.76{\pm}0.3(J,\; KT-DM{\beta}CD)$ )> $2.61{\pm}0.5(J,\;KT-{\beta}-CD)$ )> $2.42{\pm}0.4(J,\;KT-{\alpha}-CD)$ at pH 4.0. The in crease in permeability of $KT-DM{\beta}CD$ inclusion complex was 2.6 folds in the J and 4.5 folds in the N when the perfusing solution was changed from the buffer(pH 4.0) to saline. The absorption rate of $KT-DM{\beta}CD$ inclusion complex after nasal administration was more rapid than those of ketoconazole alone and $KT-DM{\beta}CD$ inclusion complex after oral administration to rats. In comparision with an oral administration of ketoconazole suspension in corn oil, the relative bioavailability was calculated 137.3% for the oral and 195.0% for nasal $KT-DM{\beta}CD$ inclusion complex in rats. The present results suggest that $KT-DM{\beta}CD$ inclusion complex may serve as a potential nasal absorption enhancer for the nasal delivery of ketoconazole.
Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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v.31
no.2
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pp.56-60
/
2020
Vocal fold injections are usually performed with a patient wake in an office under local anesthesia. For comfortable and safe office-based procedures, thorough anesthesia and premedication should be provided to the following three regions; nasal cavity, oropharynx, and larynx. Topical lidocaine is most widely used anesthetics on office based procedure. Lidocaine has a low to intermediate potency, 45 minutes to 60 minutes' duration of action, and onset of sufficient anesthesia within 90 seconds of topical administration. Tetracaine, prilocaine, ropivacaine, and bupivacaine also have been used in the office-based procedures. Nasal decongestant, oxymetazoline, is also used for widening nasal cavity by constriction of nasal mucosa. The amount of topical and local anesthetics used in vocal fold injection rarely exceeds toxic doses. The physician should know proper anesthesia techniques and must be familiar with the safe dose and complication of all anesthetics used.
Journal of Korean Academy of Nursing Administration
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v.19
no.1
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pp.87-94
/
2013
Purpose: The purpose of this study was to provide a basis for non-humidified low flow oxygen by nasal cannula and to provide a guide for consistent care in nursing practice. Methods: A methodological study on the development of guidelines with experts' opinions on collected items, framing PICO questions, evaluating and synthesizing texts which were searched with the key words (low flow oxygen, nasal cannula, humidification of oxygen, guideline) from web search engines. Results: Of the 45 researched texts on the web, 9 texts relevant to the theme were synthesized and evaluated. All patients with humidified or non-humidified oxygen therapy reported that they had no discomfort. Conclusion: The results indicate that there are no tangible grounds for patients' perceived differences between the humidified and non-humidified oxygen under 4L/min supplied by nasal cannula. with oxygen. Therefore, non-humidification oxygen therapy is strongly advised when suppling under 4L/min oxygen by nasal cannula (recommended grade A).
The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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v.18
no.2
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pp.36-50
/
2005
Background and Objectives: Allergic rhinitis is an allergic reaction characterized by sneezingm itchy nose, mouth and throat, congestion and/or nasal discharge. The offending allergenes are usually pollens, molds, dust mites and animal allergen. Recently, the incidence of infectious nasal diseases tend to decrease. However, allergic rhinitis has increased and treatment in most cases has only deat with the symptom. Tongkyu-tang was composed of sixteen crude drugs. The Oriental Medical References mention therapeutic effects of Tongkyu-tang on nasal obstruction, watery nasal discharg. And Tongkyu-tang has clinically been used for the treatment of common cold, headache, sternutation, rhinitis etc. Speacially Tongkyu-tang is one of the most frequently used medical treatment for the allergic rhinitis. Experimental studies were conducted to investigate for the effect of Tongkyu-tang on the changes of neutrophil segment, lymphocyte, total IgE and nassal tissue in allergic rhinitis of ovalbumin-inhalation rat. Meterial and Methods: Fifteen Sprague-Dawley rats were divided into three group: normal group, control group, experimental group. To induce the allergic rhinitis in control group and experimental group, rats were sentitized intraperitoneally with 0.1 % ovalbumin solution 3 times at intervals of I week. Then intranasal sensitization was performed by diffusing 0.1 % ovalbumin solution 3 times at intervals of 2 days. After that time, rat in the experimental group were oral administration treated by Tongkyu-tang for 28 days. We observed changes in nasal tissue; changes in the number of white blood cell, red blood cell and total Ig E; also changes in the segment of neutrophil and lymphocyte in blood. And we observed the changes of AST, ALT of three group. We used anova test statistically. Result: The number of leucocyte remained unchanged between three group. The number of erythrocyte was increased in experimental group and control group when compared with the normal group. The segment of neutrophil, in blood was decreased in experimental group when compared with the control group but, that was not significant statistically(p<0.05). The promotion of lymphocyte in blood was significantly decreased in experimental group when compared with the Control group(p<0.05). Total IgE was decreased in experimental group when compared with the control group but, that was not significant statistically(p<0.05). The cilium be well preserved in experimental group: the nasal tissue in experimental group was similar to in the normal group. Congestion and expantion of grandular cell in nasal submucosa, hypertropy of epithelium in nasal mucosa, acid mucus in epithelium and neutral mucus in subepithelium were decreased in experimental group when compared with the control group. Effect of Tongkyu-tang on the liver function were also studies in rats. Treatment of Tongkyu-lang did not affected on AST and ALT. Conclusion: Considering the above experimental results, it is suggested that oral administration treatment using Tongkyu-lang, without worry about liver function injury, decreased response on an Animal model with Allergic Rhinitis.
The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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v.21
no.3
/
pp.111-123
/
2008
Objectives : We aimed to investigate therapeutic effect of Bojungikgitang-gamibang(BI) and Mahwangshingungsan(MS) by observing changes in blood cells and the nasal mucosa of Sprague-Dawley(SD) rats with allergic rhinitis. Methods : Twenty-four SD rats were divided into three groups: normal, control, and sample group. Allergic rhinitis was induced in the control and sample group by intraperitoneal and intranasal sensitization with 0.1% and 0.4% Ovalbumin solution. Then BI was orally administered only to the sample group along with MS for 28days, while the rats in the control group was given normal saline. Results : BI and MS showed significantly decreased IgE level on the serum of the rat model, Bl and MS showed significantly decreased eosinophil level on the blood of the rat model. BI and MS inhibited the inflammatory reaction on the nasal mucosal tissue, according to nasal mucosal biopsy. Bl and MS had anti-allergic according to level, eosinophil level, nasal mucosal biopsy. BI and MS had no hepatoxicity, according to AST and ALT on the serum. Conclusion : According to the above results, it is considered that Bl and MS is helpful in treatment of allergic rhinitis.
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