SEARCH · PubMed Health

Results for “Administration, Intranasal”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources

PubMed1994

Intranasal delivery of cardiovascular agents: an innovative approach to cardiovascular pharmacotherapy.

The intranasal administration of drugs has long been used for the topical treatment of various nasal disorders. Many features of the intranasal mucosa also make it useful for delivery of systemically active agents. It has been shown that intranasal drug administration can provide plasma drug levels similar to those observed with comparable doses of parenteral drugs. The feasibility of intranasal administration of propranolol, nifedipine, and nitroglycerin has been investigated in several small clinical studies. Intranasal propranolol has been shown to improve exercise tolerance in patients with angina pectoris. Intranasal nifedipine has been used to treat patients with perioperative hypertension and hypertensive crisis. Intranasal administration of nitroglycerin was shown to blunt the hypertensive response to endotracheal intubation. These studies and others suggest that intranasal delivery of cardiovascular drug treatment could be used in those clinical situations where a rapid or intermittent drug effect is desired and can potentially serve as an alternative to parenteral drug administration.

Absorption↗

PubMed1998

Enhancement of immune response to intranasal influenza HA vaccine by microparticle resin.

We evaluated the potential application of ion-exchange resins for the enhancement of intranasal immune response to influenza HA vaccine in mice. Female Balb/c mice were intranasally immunized with inactivated influenza HA vaccine with one of four kinds of resin microparticles: sodium polystyrene sulfonate, calcium polystyrene sulfonate, polystyrene benzyltrimetylammonium chloride, or polystyrene divinylbenzene. Haemagglutinin-inhibiting antibodies were measured in the serum and IgA antibodies in the nasal wash after 4 weeks. The results demonstrated that intranasal administration of influenza HA vaccine in combination with the 20-45 microns sized particles of sodium polystyrene sulfonate resin induced the highest levels of mucosal IgA, and enhanced systemic haemagglutinin-inhibiting antibodies. While the Th2-type cytokine IL-4 was detected in the sera after intranasal immunization with HA vaccine and sodium polystyrene sulfonate, neither IFN-gamma nor IL-2 could be detected. Furthermore, mice intranasally immunized with HA vaccine together with sodium polystyrene sulfonate resin showed higher protection against viral challenge than those that received HA vaccine alone. Intranasal administration of influenza HA vaccine with sodium polystyrene sulfonate resin might be both a safe and an effective means of immunization.

Administration, Intranasal↗

PubMedDate not supplied

[Mucosal viral vaccines: progress and problems].

Data obtained in the recent years on developing the viral inactivated mucosal vaccines by applying the mucosal-adhesive adjuvants are presented in the survey. Progress achieved in designing the mucosal influenza vaccines and mucosal vaccines against a variety of other viral infections is pointed out. Cross-protection against variations of a virus within its subtype limits as well as overcoming of a negative influence of parent antibodies produced on the immunogenicity of live-vaccines', which were used at young age, were observed in the intranasal administration of viral mucosal vaccines. A number of shortcomings of bacterial toxins used as mucosal-adhesive adjuvants as well as problems, which may arise when the viral mucosal vaccines are used on a large-scale basis due to a need in their two- and-threefold intranasal administration, are in the focus of attention.

Adhesives↗

PubMed1997

Intranasal immunization of a DNA vaccine with IL-12- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing plasmids in liposomes induces strong mucosal and cell-mediated immune responses against HIV-1 antigens.

A DNA vaccine constructed with the CMV promoter conjugated to env gp160 and rev genes has been shown to induce an effective Th1-type immune response when inoculated via an intramuscular route. In the present study, we obtained high levels of both humoral and cell-mediated immune activity by intranasal administration of this DNA vaccine. The production of mucosal IgA Ab in feces and vaginal fluid was stimulated significantly by intranasal DNA administration. This route of administration resulted in a significant level of HIV-1-neutralizing Abs in feces and serum. Cytokine assays revealed that intranasal administration of this DNA vaccine induces a Th2-type immune response. Interestingly, cationic liposomes greatly enhanced these activities. Abs against HIV-1 were present for at least 10 mo. Coadministration of the DNA vaccine with IL-12- and granulocyte/macrophage-CSF-expressing plasmids induced high levels of HIV-specific CTLs and an increase in delayed type hypersensitivity when administered by the intranasal route. These results clearly demonstrate that intranasal administration of this DNA vaccine with liposomes, together with IL-12- and/or granulocyte/macrophage-CSF-expressing plasmids, induces a strong level of anti-HIV-1 immune response.

Administration, Intranasal↗

PubMed1989

Cocaine-induced coronary-artery vasoconstriction.

Intranasal cocaine is used frequently as a local anesthetic during many rhinolaryngologic procedures. Although its "recreational" use in high doses has been associated with chest pain and myocardial infarction, this association has not been established when cocaine is used in low doses as a topical anesthetic, and its effect on the coronary vasculature of humans is unknown. We studied the effects of intranasal cocaine (10 percent cocaine hydrochloride; 2 mg per kilogram of body weight) on the blood flow in and dimensions of the coronary arteries and on myocardial oxygen demand in 45 patients (34 men and 11 women, 36 to 67 years of age) who were undergoing cardiac catheterization for the evaluation of chest pain. Heart rate, arterial pressure, blood flow in the coronary sinus (measured by thermodilution), and the dimensions of the epicardial left coronary artery (measured by quantitative arteriography) were measured before and 15 minutes after the intranasal administration of saline (in 16 patients) or cocaine (in 29). No variables changed after the administration of saline. After cocaine was administered, the heart rate and arterial pressure rose, the coronary-sinus blood flow fell (from a mean [+/- SD] of 149 +/- 59 ml per minute to 124 +/- 53 ml per minute), and the diameter of the left coronary artery decreased by 8 to 12 percent (P less than 0.01 for all comparisons). No patient had chest pain or electrocardiographic evidence of myocardial ischemia after the administration of cocaine. Subsequently, the administration of the alpha-adrenergic blocking agent phentolamine caused all these values to return to base-line levels. There was no difference in response between the patients found to have disease of the left coronary artery (n = 28) and those without such disease (n = 17). We conclude that the intranasal administration of cocaine near the dose used for topical anesthesia causes vasoconstriction of the coronary arteries, with a decrease in the coronary blood flow, despite an increase in myocardial oxygen demand, and that these effects are mediated by alpha-adrenergic stimulation. It is reasonable to assume that these effects would be more pronounced at the much higher doses associated with the recreational use of cocaine.

Administration, Intranasal↗

PubMedDate not supplied

Metabolic effects of intranasally administered glucagon: comparison with intramuscular and intravenous injection.

Intranasal administration of glucagon, 1 mg, plus sodium glycocholate 15 mg as a surfactant, raised blood glucose levels and plasma levels of immunoreactive glucagon (IRG) and immunoreactive insulin (IRI). Spray solutions were more effective than drops, and neither the surfactant alone nor glucagon alone had any effect. Blood glucose levels were similarly affected by intravenous glucagon, while intramuscular glucagon was slightly more effective. The highest IRG concentrations were reached after intravenous administration, while intramuscular injection of glucagon was accompanied by the highest IRI release. These data indicate that intranasal administration of glucagon exerts metabolic effects similar to intramuscular and intravenous administrations. Further studies are needed to improve bioavailability and efficacy of intranasally administered glucagon.

Administration, Intranasal↗

PubMed1992

Expression of the OSU rotavirus outer capsid protein VP4 by an adenovirus recombinant.

Full-length cDNA of the VP4 gene of porcine rotavirus strain OSU was cloned into adenovirus type 5 (Ad5) downstream of the E3 promoter. The plaque-purified recombinant (Ad5-OSU VP4) expressed apparently authentic VP4 rotavirus outer capsid protein. The protein had the same molecular size (85 kDa) and electrophoretic mobility as did native OSU VP4 and was immunoprecipitated by a polyclonal antiserum raised to OSU VP4. Cotton rats that possessed prechallenge rotavirus antibodies that may have been acquired either passively or actively developed neutralizing antibodies against the OSU strain following intranasal administration of the live Ad5-OSU VP4 recombinant. The neutralizing activity was enhanced by a parenteral booster injection with baculovirus-expressed OSU VP4 antigen. In addition, a high titer of neutralizing antibodies was induced by parenteral administration of the latter antigen and subsequent intranasal administration of the Ad5-OSU VP4 recombinant. These observations indicate that the VP4 outer capsid protein of a rotavirus strain can be expressed by a recombinant adenovirus vector. This approach warrants further exploration for immunization against rotavirus disease.

Adenoviruses, Human↗

PubMedDate not supplied

[An experimental substantiation for using the "Semax" neuroprotector in the treatment of optic-nerve diseases].

In order to substantiate the feasibility of using the "Semax" neuroprotector in the treatment of optic-nerve diseases its pharmacokinetics in the intranasal administration was studied in experiments with rats; besides, the physical-and-chemical properties of "Semax" were investigated to define the preparation's stability and mobility in the electric field. A series of experiments, involving a tritium-marked "Semax", showed that the peptide actively penetrates into the brain and eyes of experimental animals after its intranasal administration. It was established, within a study aimed at determining the electrophoretic activity and stability of "Semax" in the electric field, that the preparation does not disintegrate in the electric field, it posses the electrophoretic mobility and moves, in the electric field, from plus to minus; therefore, the "Semax" solution must be fed from anode while making the electrophoresis procedure.

Administration, Intranasal↗

PubMed1991

Intranasal bioavailability of insulin powder formulations: effect of permeation enhancer-to-protein ratio.

The intranasal administration of powder formulations containing insulin and the permeation enhancer sodium tauro-24,25-dihydrofusidate (STDHF) were investigated in the sheep model. Both the hypoglycemic response and the serum insulin levels increased as the mole ratio of STDHF to insulin was increased from 0 to 16.8. In vitro dissolution rates of the powders and the rapid tmax (approximately 5 min) observed after intranasal administration suggest that the absorption of insulin is not dissolution limited. The bioavailabilities (F) of the powder formulations ranged from 2.9 to 37.8%. In comparison, the F values for a solution formulation with a STDHF:insulin ratio of 8.4 administered as either drops or spray were 15.7 and 37.4%, respectively. The permeation enhancer STDHF increases mucosal permeability and reduces the average molecular weight of the insulin species.

Absorption↗

PubMed1994

Comparison of two software programs to be used for the calculation of population pharmacokinetic parameters.

The pharmacokinetic parameters of apomorphine, a potent dopamine agonist, were calculated after subcutaneous and intranasal administration. Two available software packages for TDM were used (USC*PACK and MW/PHARM). The findings for the calculated parameters Kel, Vslope, Ka and bioavailability were compared. Although small, sometimes significant differences were found, the NPEM program from the USC*PACK collection provides most information about the population under investigation. We found a median Vslope of 1.7408 +/- 0.8461 (S.D.) 1/kg, and a mean Kel of 1.5341 +/- 0.3748 h-1. The absorption after intranasal administration was extremely rapid: Ka = 20.5 +/- 1.96 h-1, comparable with that found with subcutaneous absorption: Ka = 23.04 +/- 2.20 h-1.

Administration, Intranasal↗

PubMedDate not supplied

[Development of mucosal influenza inactivated vaccines].

In this review recent data on the development of mucosal influenza inactivated vaccines with the use of mucosoadhesive adjuvants are presented. After the intranasal administration of such vaccines the formation of not only systemic, but also local immunity (IgA antibodies), as well as cross protection against the variants of influenza virus within its serotype, can be observed. Some mucosal influenza vaccines have passed clinical tests. Certain drawbacks of Escherichia thermolabile enterotoxin, used as mucosoadhesive adjuvant, and difficulties which may arise in mass immunization with mucosal vaccines due to the necessity of introducing them in two or three intranasal administrations are indicated.

Adjuvants, Immunologic↗

PubMed2005

Distribution of zolmitriptan into the CNS in healthy volunteers: a positron emission tomography study.

OBJECTIVE: Triptans are highly effective in the treatment of migraine. Both central and peripheral mechanisms of action have been suggested. Until now, firm data about the passage of triptans into the CNS in humans have been lacking. The aim of the current study was to evaluate, using positron emission tomography (PET), the uptake and distribution of zolmitriptan into the CNS after intranasal administration. SUBJECTS AND METHODS: Eight healthy volunteers, five males and three females (mean ages 23 and 26 years, respectively), were included. Radioactive [carbonyl-11C]zolmitriptan was infused intravenously for 5 minutes on two occasions: once alone, and once 30-40 minutes after intranasal administration of unlabelled zolmitriptan 5 mg. PET was used to measure the concentration of labelled zolmitriptan in the brain, from the start of the tracer infusion for 90 minutes. Regional cerebral blood volume was determined with [15O]carbon monoxide. In addition, an MRI scan was performed to obtain anatomical information. The PET images were analysed quantitatively for different areas of the brain, generating [11C]zolmitriptan time-activity data corrected for circulating tracer activity. The rate of uptake of intranasal zolmitriptan into the CNS was estimated by kinetic modelling using the PET data. RESULTS: PET data from this study demonstrate a rapid dose-proportional uptake of [11C]zolmitriptan into the brain. Significant concentrations of [11C]zolmitriptan were found in all brain regions studied. Calculated CNS concentrations after intranasal zolmitriptan administration showed a gradual increase, reaching about 2 nM (0.5 microg/L) 30 minutes after administration and 3.5 nM (1.0 microg/L), or one-fifth of the plasma concentration, 1 hour after administration. Five minutes after zolmitriptan administration, the mean CNS concentration had already reached 0.5 nM, which is higher than in vitro values for initiation of the agonistic action on 5-HT(1B/1D) receptors. CONCLUSION: This study demonstrates by direct measurements that zolmitriptan enters the brain parenchyma in humans, achieving an uptake rate and concentration compatible with a central mode of action.

Administration, Intranasal↗

PubMed2003

Nonclinical safety evaluation of Escherichia coli heat-labile toxin mucosal adjuvant as a component of a nasal influenza vaccine.

Conventional influenza vaccines currently in use are administered parenterally and generally confer good protection against systemic disease through the induction of high titers of serum virus-neutralizing antibodies. Parenteral vaccines are suboptimal in that they fail to induce a local mucosal response that may prevent the early stages of virus infection. Thus, the intranasal administration of a vaccine may provide a viable alternative to the parenteral route. Indeed, intranasal administration of vaccine antigens when formulated with an appropriate mucosal adjuvant (e.g., bacterial toxins), results in a vigorous local and systemic immune response. This review discusses the nonclinical safety evaluation of Escherichia coli heat-labile toxin as a mucosal adjuvant for an intranasally administered influenza vaccine.

Adjuvants, Immunologic↗

PubMed2004

Insulin and the CNS: effects on food intake, memory, and endocrine parameters and the role of intranasal insulin administration in humans.

Insulin is mainly known for its peripheral effects on the metabolism of glucose, fats, and proteins. However, insulin also exerts important actions within the brain, and functions as a neuropeptide. The brain can thus be regarded as both an insulin-sensitive and a glucose-sensitive organ. Its neuroanatomical basis is the localization of insulin receptors, predominantly in the olfactory bulbs, hypothalamus, and hippocampus. Data obtained in animal experiments reveal an interesting insulin profile in the brain. Central insulin affects glucoregulation. As long as peripheral euglycemia is maintained, it was shown to reduce food intake and body weight and to improve learning and memory. Cognitive dysfunctions in dementia of the Alzheimer type (DAT) are associated with insulin deficiency within the brain, and memory improves in DAT patients when insulin levels increase. After describing these actions of insulin in the brain, we address here the transport of insulin into the brain. Insulin can either be transported from the periphery to the brain, or be administered directly into the brain. To reach insulin receptors directly, animals are typically administered insulin via the cerebral ventricles. For humans, the intranasal route is a practicable way to reach the brain while maintaining euglycemia. Additionally, the localization of insulin receptors in the olfactory bulb makes insulin interesting for the nose-to-brain pathway. Promising initial results have been reported with intranasally administered insulin corresponding to the diverse actions of insulin in the brain. Interestingly, initial data indicate that states of central insulin deficiencies (DAT and obesity) are accompanied by olfactory deviations. Thus, the nose-to-brain pathway deserves further attention.

Administration, Intranasal↗

PubMed2000

Neutrophil recruitment and increased permeability during acute lung injury induced by lipopolysaccharide.

The intranasal administration of lipopolysaccharide (LPS) to mice triggers a huge influx of polymorphonuclear neutrophils (PMNs) into the airway spaces, with a peak at 48 h. The increase in protein concentration, an index of microvascular permeability, displayed a different pattern, i.e., a first increase with a plateau between 3 and 24 h followed by a second increase peaking at 72 h. When mice were depleted of circulating PMNs, the increase in protein concentration was inhibited at 3 h but not at 24 h. The lack of PMN involvement at 24 h was confirmed by 1) in situ activation of exudated PMNs present in the air spaces on intranasal administration of LPS and 2) induction of the migration of PMNs sequestered in lung vessels on intraperitoneal administration of LPS. These findings show that the increase in microvascular permeability during lung inflammation is due to at least two distinct mechanisms, an early one related to the neutrophil influx and a delayed one occurring even under neutropenic conditions.

Acute Disease↗

PubMed2003

Somato-sympathetic vasoconstriction to intranasal fluid administration with consecutive decrease in nasal nitric oxide.

AIM: Patients suffering from non-allergic chronic rhinosinusitis (NACRS) increasingly use intranasal saline sprays. They report better nasal comfort. METHODS: In order to better understand this phenomenon, we studied intranasal laser Doppler flowmetry (LDF) and nasal nitric oxide (NO) variations evoked by local administration of saline, histamine, N-acetylcysteine (NAC) and lidocaine at room temperature (22 degrees C). RESULTS: There was a significant (P < 0.05) 14 +/- 3.8% decrease in LDF signal after 30 s, which lasted for 60-90 s, for all the substances applied at 22 degrees C. This pharmaco-independent vasoconstriction was further studied in patients under general anaesthesia (GA), with saline at 37 degrees C and after intranasal adrenaline treatment. While GA did not influence the vasoconstriction, saline at 37 degrees C and adrenaline pre-treatment abolished it. Nasal NO is influenced by vasoconstriction. Therefore we investigated, whether the observed vasoconstriction also changes nasal NO. A significant (P < 0.001) 8.03 +/- 0.59% decrease in nasal NO was recorded 60 s after administration of all the substances, and under GA after 22 degrees C saline application. This NO decrease was absent after intranasal adrenaline pre-treatment. An additional experiment tested the effect of nose blowing on nasal NO concentration. We registered an NO decrease with a similar pattern than observed with the other substances. CONCLUSIONS: Intranasal fluid nebulization at 22 degrees C induces a sympathetic mediated, transient vasoconstrictor reflex response. This somato-sympathetic vasoconstriction induces a decrease in nasal NO. Both could be related to the subjective comfort experienced by NACRS patients using intranasal saline sprays.

Acetylcysteine↗

PubMed2004

Intranasal atrial natriuretic peptide acts as central nervous inhibitor of the hypothalamo-pituitary-adrenal stress system in humans.

Increased hypothalamo-pituitary-adrenal activity contributes to morbidity in widespread metabolic and psychiatric diseases. Inhibition of hypercortisolism represents a promising therapeutic strategy in these conditions, which currently cannot be used. Here, we tested the hypothesis that atrial natriuretic peptide (ANP) administered intranasally is a safe and feasible inhibitor of pituitary-adrenal activity at the central nervous level. Thirty minutes after intranasal administration of ANP (1 mg) and placebo, pituitary-adrenal activity was stimulated in 18 healthy men by two tests: 1) a standard insulin-hypoglycemia test and 2) CRH combined with vasopressin (VP), respectively. ACTH, cortisol, VP, blood pressure, heart rate, and measures of fluid balance were also recorded. Pretreatment with ANP suppressed cortisol (P < 0.01) and ACTH (P < 0.05) secretory responses to insulin-induced hypoglycemia to about half of that seen after placebo, but pituitary-adrenal activity was not suppressed by CRH/VP injection (P > 0.7). Indicators of fluid balance, cardiovascular parameters, and self-report measures were not influenced by the treatment. Results indicate a strong inhibition of stimulated pituitary-adrenal activity after intranasal administration of ANP. The absence of an effect on CRH/VP-induced pituitary-adrenal responses suggests a direct action of the peptide on the central nervous system inhibiting stimulated hypothalamo-pituitary-adrenal activity at the hypothalamic level.

Administration, Intranasal↗

PubMed1992

Urinary excretion of ephedrine after nasal application in healthy volunteers.

The urinary excretion of ephedrine after intranasal administration of the drug was studied in 8 healthy volunteers. Ephedrine (6 drops of a commercial 0.75% nasal ephedrine solution in each nasal cavity) was administered 4 times at intervals of 2 h (total amount applied equivalent to approximately 14 mg ephedrine), and urine was collected each hour for 10 h; the volunteers exercised on a bicycle ergometer at 50% of their VO2max for 2 h after the last ephedrine application. Ephedrine was detected in all urine samples. The urinary ephedrine concentration ranged from 0.9 to 16.5 micrograms mL-1; the number of urine samples with an ephedrine concentration exceeding 5 micrograms mL-1 ranged from 1/10 (volunteer 2) to 9/10 (volunteers 1 and 3). The mean percentage of dose recovered within 10 h was 33% (range 23-50%). There was a weak but significant negative correlation between urinary pH and amount of ephedrine in the urine; exercise did not consistently influence the urinary amount. These results illustrate the systemic availability of ephedrine upon intranasal administration and show that the therapeutic use of a nasal ephedrine formulation by an athlete on the day of a competition can lead to a urinary ephedrine concentration above 5 micrograms mL-1, which is considered positive in current doping regulations of the International Union of Cyclists.

Administration, Intranasal↗