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PubMed1993

Safety and effectiveness of intranasal administration of sedative medications (ketamine, midazolam, or sufentanil) for urgent brief pediatric dental procedures.

Thirty children presenting to the dental clinic of a pediatric hospital who required brief but urgent dental care, and who could not be satisfactorily examined or treated, were administered one of three medications--ketamine (Ketalar), 3 mg/kg; midazolam (Versed), 0.4 mg/kg; or sufentanil (Sufenta), 1.5 or 1.0 micrograms/kg--intranasally in a randomized, double-blinded protocol. The patients were brought to the day surgery area following appropriate fasting and administered one of the medications diluted in a dose of 0.1 mL/kg normal saline while sitting in a nurse's arms. Cardiorespiratory monitors were applied when tolerated, and the child was placed on the operating room table. Each child was injected locally with up to one dental cartridge of 2% lidocaine with 1:100,000 epinephrine before dental extractions. A sedation score was recorded using a scale where 1 = hysterical/untreatable, 5 = ideal sedation, and 10 = obtunded and desaturated, requiring airway management assistance. Midazolam administration resulted in acceptable sedation (mean score: 4) with no desaturations below 90% as measured by pulse oximetry and a mean recovery room observation time of only 3 +/- 2 min (+/- SD). Ketamine also had a mean sedation score of 4 and a short recovery period (7 +/- 7 min); however, two children experienced brief desaturations. Sufentanil at 1.5 micrograms/kg was noted to produce much more heavily sedated children (mean score 7), with a high incidence of significant oximetry desaturation (80%) and prolonged recovery room duration (58 +/- 40 min). Use of 1.0 microgram/kg sufentanil resulted in no desaturations, less sedation (mean score 4), and a brief recovery time (7 +/- 13 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1989

Intranasal administration of deferoxamine to iron overloaded patients.

We examined the effect of intranasal administration of deferoxamine on iron excretion in seven patients with iron overload secondary to chronic transfusion therapy. Deferoxamine was administered in doses of 0.75 to 3.0 gm given over 12 hours in a variety of dosing schedules. There was a probable, though not significant, dose response relationship between the amount of iron excreted and the dose administered. The amount of iron excreted was 10%-15% of that obtained using the same dosage of deferoxamine given by the subcutaneous route over the same time period. Hourly administration was more effective than less frequent administration. Addition of taurodeoxycholate to deferoxamine did not increase its absorption as measured by the levels of iron excretion. Side effects were few and consisted mainly of mild nasal irritation and a bad taste in the mouth. Nasal administration of deferoxamine may be a useful adjunct to iron chelation in patients receiving chronic transfusion therapy, particularly in those who are noncompliant with parenteral means of administration.

Administration, Intranasal↗
PubMed2004

[Preparation and properties of 5-fluorouracil-loaded chitosan microspheres for the intranasal administration].

OBJECTIVE: To study the preparation technique and release characteristic of 5-fluorouracil loaded chitosan microspheres for the intranasal administration. METHODS: Using the liquid paraffin as the oil phase,and span-80 as the emuifier; 5-fluorouracil-loaded chitosan microspheres were achieved by emulsion-chemical crosslink technique. The orthogonal experimental design was applied to optimize the preparation procedure. Dynamic dialysis method was used to determine the releasing characteristic of microspheres in vitro and it influencing factors. Swelling behavior was expressed by swelling ratio. The degree of mucoadhesion was investigated by determining the mucociliary transport rate(MTR) of the microparticle across a frog palate. RESULTS: Microspheres with a good shape and narrow size distribution were prepared. The average diameter was (43+/-4) microm. The drug loading was 38.5%+/-1.0%. The entrapment efficiency was 79.0%+/-1.8%. The drug release profile in vitro could be described by Higuichi equation Q=0.1035t(1/2)+0.0284 (r=0.9965). Chitosan had good mucoadhesive property and caused a significant reduction in MTR(P<0.01). CONCLUSION: The optimized preparation technique is stable and has a high entrapment efficiency. So it could be used to prepare 5-fluorouracil-loaded chitosan microspheres for the intranasal administration. Chitosan is a good material for nasal preparation and has prospective development in the pharmaceutical field.

Adhesiveness↗
PubMed1998

Homologous and heterologous protection after single intranasal administration of live attenuated recombinant Bordetella pertussis.

While single-dose mucosal immunization is best achieved by the use of attenuated live microorganisms, attenuation generally results in decreased immunogenicity. We attenuated Bordetella pertussis by the deletion of the pertussis toxin gene. A single intranasal administration of this strain protected against subsequent challenge as well as did the parent strain and better than immunization with commercial vaccine. Unexpectedly, this attenuation resulted in increased immunogenicity against the protective antigen filamentous hemagglutinin (FHA). In addition, immunogenicity was also enhanced against the Schistosoma mansoni Sm28GST genetically fused to FHA, resulting in protection against the parasite, as characterized by a reduction in worm burden and egg charge, after a single intranasal administration. Thus, attenuated recombinant B. pertussis strains are promising vectors for the simultaneous protection against pertussis and heterologous diseases by a single intranasal administration.

Adhesins, Bacterial↗
PubMed2004

Intranasal administration of interferon beta bypasses the blood-brain barrier to target the central nervous system and cervical lymph nodes: a non-invasive treatment strategy for multiple sclerosis.

Intranasal (i.n.) administration of IFN beta-1b was examined as a route for targeted delivery to the rat central nervous system (CNS). Intranasal administration resulted in significant delivery throughout the CNS and cervical lymph nodes with low delivery to peripheral organs. At similar blood levels, intravenous (i.v.) administration of IFN beta-1b yielded 88-98% lower CNS levels and 100-1650% greater peripheral organ levels compared to intranasal. Autoradiography confirmed much greater delivery to the CNS with intranasal administration. Intranasally administered IFN beta-1b reached the brain intact and produced tyrosine phosphorylation of IFN receptor in the CNS. Intranasal administration offers a non-invasive method of drug delivery for multiple sclerosis (MS) that bypasses the blood-brain barrier (BBB) and directly targets the CNS and lymph nodes.

Administration, Intranasal↗
PubMed1979

Luteolytic effect of intranasal administration of [D-Ser(TBU)6,DES-Gly-NH2(10)]-luteinizing hormone-releasing hormone ethylamide in normal women.

Intranasal administration of two doses of potent agonist of luteinizing hormone (LH)-releasing hormone (LHRH), [D-Ser(TBU)6,des-Gly-NH2(10)]LHRH ethylamide (500 micrograms), a 8 A.M. and 5 P.M. on 1 day between day 4 and 9 following the LH peak in six normal women during two consecutive menstrual cycles shortened the luteal phase from 13.6 +/- 0.3 days to 10.9 +/- 0.3 days (mean shortening, 2.7 days; range, 0.5 to 4.5 days) and reduced plasma progesterone levels to 61.3% +/- 9.2% of control. Hormone changes were followed by daily measurements of plasma LH, follicle-stimulating hormone, 17 beta-estradiol, and progesterone during two pretreatment cycles, two treatment cycles, and two post-treatment cycles. No side effect was observed, and apparently normal cycles occurred immediately after treatment. The present data indicate that the intranasal administration of a potent LHRH agonistic analog can induce luteolysis and control time of occurrence of menses in normal women. This finding opens the possibility of a new and physiologic approach to fertility control.

Administration, Intranasal↗
PubMed2002

Effect of intranasal administration of CV-11974, a type 1 angiotensin II receptor antagonist, on airway hyperresponsiveness and airway inflammation induced by antigen inhalation in guinea pigs.

BACKGROUND: Angiotensin II is a putative mediator in asthma, but the effect of topical administration of type 1 angiotensin II (AT1) receptor antagonists on allergic airway reactions is not known. OBJECTIVE: To investigate the effect of intranasal administration of CV-11974, an AT1 receptor antagonist, and of PD123319, a type 2 angiotensin II (AT2) receptor antagonist, on antigen-induced airway reactions in guinea pigs. METHODS: Thirty minutes after intranasal topical administration of CV-11974 (0.1 or 1.0 mg/ml) or PD123319 (10 mg/ml) into the airways, the animals were given an antigen challenge. Airway hyperresponsiveness and bronchoalveolar lavage fluid were analyzed 24 h after the antigen challenge. RESULTS: Although these compounds did not inhibit antigen-induced early-phase bronchoconstriction or late-phase airway eosinophilia, intranasal administration of CV-11974 (but not PD123319) inhibited antigen-induced airway hyperresponsiveness in a dose-dependent manner 24 h after the antigen challenge. CONCLUSION: Intranasal administration of an AT1 receptor antagonist reduces antigen-induced airway hyperresponsiveness.

Administration, Inhalation↗
PubMed2000

Activity-dependent neurotrophic factor: intranasal administration of femtomolar-acting peptides improve performance in a water maze.

Activity-dependent neurotrophic factor (ADNF) is a glia-derived protein that is neuroprotective at femtomolar concentrations. A nine-amino acid peptide derived from ADNF (Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala; ADNF-9) captured the activity of the parent protein and has been reported to protect cultured neurons from multiple neurotoxins. Antibodies recognizing ADNF-9 produced neuronal apoptosis, and identified an additional, structurally related, glia-derived peptide, Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (NAP). Previous comparative studies have characterized s.c.-injected NAP as most efficacious in protecting against developmental retardation and learning impairments in apolipoprotein E-deficient mice. This study was designed to assess 1) neuroprotection after intranasal administration of ADNF-9 and NAP to rats treated with the cholinotoxin ethylcholine aziridium; and 2) bioavailability and pharmacokinetics after intranasal administration. Results showed significant improvements in short-term spatial memory, as assessed in a water maze, after daily intranasal administration of 1 microg of peptide (ADNF-9 or NAP) per animal. However, a 5-day pretreatment with ADNF-9 did not improve performance measured after cessation of treatment. Compared with rats treated with ADNF-9, NAP-pretreated animals exhibited a significantly better performance. Furthermore, NAP (and not ADNF-9) protected against loss of choline acetyl transferase activity. Significant amounts of (3)H-labeled NAP reached the brain, remained intact 30 min after administration, and dissipated 60 min after administration. This study revealed efficacy for ADNF-related peptides in rodent models for neurodegeneration. The small size of the molecules, the low dosage required, the noninvasive administration route, and the demonstrated activity in a relevant paradigm suggest NAP as a lead compound for future drug design.

Administration, Intranasal↗
PubMedDate not supplied

Neurologic complications following intranasal administration of heroin in an adolescent.

OBJECTIVE: To describe an adolescent patient who developed a stroke following intranasal administration of heroin. CASE SUMMARY: A 17-year-old adolescent with no prior medical problems "snorted" an unknown quantity of heroin. The patient developed respiratory failure, shock, and seizures. When he regained consciousness, the patient had evidence of hypoxic-toxic encephalopathy on neuropsychologic examination. Magnetic resonance imaging revealed an infarct in the globus pallidus region of the brain. DISCUSSION: Serious neurologic complications following intranasal administration of heroin have been reported rarely in children. Correlations between findings on neuropsychologic examination and magnetic resonance imaging following drug overdoses have likewise been rarely described. We reviewed literature pertaining to the etiology, pharmacology, and pathophysiology of neurologic complications resulting from heroin intoxication. CONCLUSIONS: As the use of intranasal heroin is increasing in the pediatric population, healthcare professionals should be aware of the various potentially serious complications that may occur.

Administration, Intranasal↗
PubMed2001

Effect of intranasal administration of Lactobacillus casei Shirota on influenza virus infection of upper respiratory tract in mice.

In mice administered Lactobacillus casei strain Shirota (LcS) intranasally, potent induction of interleukin 12, gamma interferon, and tumor necrosis factor alpha, which play a very important role in excluding influenza virus (IFV), was evident in mediastinal lymph node cells. In this model of upper respiratory IFV infection, the titers of virus in the nasal wash of mice inoculated with 200 microg of LcS for three consecutive days (LcS 200 group) before infection were significantly (P < 0.01) lower than those of mice not inoculated with LcS (control group) (10(0.9 +/- 0.6) versus 10(2.1 +/- 1.0)). The IFV titer was decreased to about 1/10 of the control level. Using this infection model with modifications, we investigated whether the survival rate of mice was increased by intranasal administration of LcS. The survival rate of the mice in the LcS 200 group was significantly (P < 0.05) greater than that of the mice in the control group (69% versus 15%). It seems that the decrease in the titer of virus in the upper respiratory tract to 1/10 of the control level was important in preventing death. These findings suggest that intranasal administration of LcS enhances cellular immunity in the respiratory tract and protects against influenza virus infection.

Administration, Intranasal↗
PubMed1997

Pharmacokinetics and pharmacodynamics of midazolam after intranasal administration.

This study aimed to characterize the pharmacokinetics and pharmacodynamics of midazolam after intranasal administration to healthy volunteers. Eight participants were given 0.25 mg/kg intranasally and 2 mg intravenously in a randomized, crossover fashion. Blood samples for determination of plasma concentrations of midazolam and measures of cognitive function (using the digit symbol substitution test) were obtained at baseline and 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, and 360 minutes after administration of study medications. Plasma samples were analyzed by gas chromatography (% coefficient of variation < 10%). Pharmacokinetic data were fitted using iterative two-stage analysis to a two-compartment model. Pharmacodynamic data were fitted by a baseline subtraction Hill-type model. The mean (SD) for total clearance, distributional clearance, volume of distribution in the central compartment, volume of distribution in the peripheral compartment, absorption rate constant, bioavailability, and half-life were 0.57 (0.26) L/hr/kg, 0.31 (0.29) L/hr/kg, 0.27 (0.14) L/kg, 0.67 (0.11) L/kg, 2.46 (1.72) hr-1, 50% (13%), and 3.1 (0.84) hours, respectively. The mean (SD) for the concentration at which the effect is half maximal (EC50) and the maximal effect or the maximal change in effect measure from baseline (Emax) were 63.1 (21.2) ng/mL and 52.8 (21.1) correct substitutions, respectively. After intranasal administration, midazolam concentrations rapidly achieve values considered sufficient to induce conscious sedation and produce predictable changes in digit symbol substitution score.

Administration, Intranasal↗