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PubMed2006

Intranasal administration of chlamydial outer protein N (CopN) induces protection against pulmonary Chlamydia pneumoniae infection in a mouse model.

Chlamydia pneumoniae is an intracellular pathogen that grows inside a vacuole, referred to as an inclusion. C. pneumoniae possess a type III secretion system (TTSS), which allows them to secrete effector molecules into the inclusion membrane and to the host cell cytosol. Proteins such as chlamydial outer protein N (CopN) that associate with the inclusion membrane are potential targets for the host's MHC-dependent antigen presentation, thereby representing ideal antigen candidates for T cell-based vaccination. The results of this study showed that intranasal immunization of BALB/c mice with heat-aggregated CopN protein and an Escherichia coli heat-labile toxin (LT) induced a strong immune response, detected as antigen-specific antibody production, lymphocyte proliferation and IFN-gamma production. Furthermore, the immunization induced statistically significant protection against intranasal C. pneumoniae challenge, the level of which correlated with the magnitude of CopN-specific lymphocyte proliferation. Both heat-aggregation of the antigen and the presence of LT adjuvant were required for maximal protective effect.

Administration, Intranasal↗

PubMed1997

Effects of frequent intranasal administration of adjuvant-combined influenza vaccine on the protection against virus infection.

In previous papers, we have shown that Escherichia coli heat-labile enterotoxin B subunit, supplemented with a trace amount of the holotoxin (LTB*) could be used as a potent adjuvant for a nasal influenza HA (haemagglutinin) vaccine in humans. The present study was designed to determine whether the effectiveness of a combined LTB*-HA vaccine could be limited by preexisting immunity to LTB and how many times the adjuvant-combined vaccine could be administered intranasally without reducing its protective efficacy in BALB/c, C3H and B10 mice. The magnitude of both nasal and serum Ab responses to HA vaccine was correlated with the degree of protection against virus infection. Higher doses of LTB*-combined vaccine were required for inducing high enough levels of anti-HA Ab responses to provide complete protection in low responder mice. Repeated pretreatments with LTB* alone (more than six times), which provided high levels of preexisting Abs to LTB, inhibited the induction of anti-HA Ab responses and reduced the protective efficacy of the adjuvant-combined vaccine. However, the LTB*-combined vaccine could be given repeatedly (about ten times) to mice without reducing the effectiveness of the adjuvant-combined vaccine. These results suggest that the LTB*-combined nasal influenza vaccine can be given to humans once every few years when an epidemic of influenza may occur.

Adjuvants, Immunologic↗

PubMed2002

Intranasal administration of a synthetic peptide vaccine encapsulated in liposome together with an anti-CD40 antibody induces protective immunity against influenza A virus in mice.

Mucosal immunity is critical for protection from viral infections. We attempted to activate mucosal cytotoxic T lymphocytes (CTLs) specific for influenza A virus nucleoprotein (NP) which play an important role in protective immunity. It has been shown that dendritic cells (DCs) activated by signaling via CD40-CD40 ligand (CD40L) interaction are required for the differentiation of naive CD8(+) T cells into antigen-specific CTLs in a non-mucosal environment. We herein inoculated mice intranasally with an anti-CD40 monoclonal antibody (anti-CD40 mAb) and NP366-374 peptide, corresponding to a CTL epitope on NP, encapsulated in liposome (liposomal NP366-374) to induce protective CTL responses against influenza A virus. Intranasal but not subcutaneous immunization with liposomal NP366-374 effectively induced mucosal immunity to reduce virus replication in the lung, suggesting that anti-CD40 mAb also functioned as a mucosal adjuvant. Interestingly, neither MHC class I- nor class II-deficient mice immunized intranasally with these materials were resistant to the infection. Since anti-CD40 mAb was considered to help replace CD4(+) T cells, another help of CD4(+) T cells are presumably required for the induction of CTL activity in the lung. This approach may prove promising for developing vaccines to induce mucosal CTL responses, and seems to highlight differences between mucosal and non-mucosal immunity.

Adjuvants, Immunologic↗

PubMed2000

Treatment of experimental (Trinitrobenzene sulfonic acid) colitis by intranasal administration of transforming growth factor (TGF)-beta1 plasmid: TGF-beta1-mediated suppression of T helper cell type 1 response occurs by interleukin (IL)-10 induction and IL-12 receptor beta2 chain downregulation.

In this study, we show that a single intranasal dose of a plasmid encoding active transforming growth factor beta1 (pCMV-TGF-beta1) prevents the development of T helper cell type 1 (Th1)-mediated experimental colitis induced by the haptenating reagent, 2,4, 6-trinitrobenzene sulfonic acid (TNBS). In addition, such plasmid administration abrogates TNBS colitis after it has been established, whereas, in contrast, intraperitoneal administration of rTGF-beta1 protein does not have this effect. Intranasal pCMV-TGF-beta1 administration leads to the expression of TGF-beta1 mRNA in the intestinal lamina propria and spleen for 2 wk, as well as the appearance of TGF-beta1-producing T cells and macrophages in these tissues, and is not associated with the appearances of fibrosis. These cells cause marked suppression of interleukin (IL)-12 and interferon (IFN)-gamma production and enhancement of IL-10 production; in addition, they inhibit IL-12 receptor beta2 (IL-12Rbeta2) chain expression. Coadministration of anti-IL-10 at the time of pCMV-TGF-beta1 administration prevents the enhancement of IL-10 production and reverses the suppression of IL-12 but not IFN-gamma secretion. However, anti-IL-10 leads to increased tumor necrosis factor alpha production, especially in established colitis. Taken together, these studies show that TGF-beta1 inhibition of a Th1-mediated colitis is due to: (a) suppression of IL-12 secretion by IL-10 induction and (b) inhibition of IL-12 signaling via downregulation of IL-12Rbeta2 chain expression. In addition, TGF-beta1 may also have an inhibitory effect on IFN-gamma transcription.

Administration, Intranasal↗

PubMed1996

Neuroprotective strategy for Alzheimer disease: intranasal administration of a fatty neuropeptide.

Neurodegenerative diseases, in which neuronal cell disintegrate, bring about deteriorations in cognitive functions as is evidenced in millions of Alzheimer patients. A major neuropeptide, vasoactive intestinal peptide (VIP), has been shown to be neuroprotective and to play an important role in the acquisition of learning and memory. A potent lipophilic analogue to VIP now has been synthesized, [stearyl-norleucine17]VIP ([St-Nle17]VIP), that exhibited neuroprotection in model systems related to Alzheimer disease. The beta-amyloid peptide is a major component of the cerebral amyloid plaque in Alzheimer disease and has been shown to be neurotoxic. We have found a 70% loss in the number of neurons in rat cerebral cortical cultures treated with the beta-amyloid peptide (amino acids 25-35) in comparison to controls. This cell death was completely prevented by cotreatment with 0.1 pM [St-Nle17]VIP. Furthermore, characteristic deficiencies in Alzheimer disease result from death of cholinergic neurons. Rats treated with a cholinergic blocker (ethylcholine aziridium) have been used as a model for cholinergic deficits. St-Nle-VIP injected intracerebroventricularly or delivered intranasally prevented impairments in spatial learning and memory associated with cholinergic blockade. These studies suggest both an unusual therapeutic strategy for treatment of Alzheimer deficiencies and a means for noninvasive peptide administration to the brain.

Administration, Intranasal↗

PubMed2000

Induction of tolerance with intranasal administration of human cartilage gp-39 in DBA/1 mice: amelioration of clinical, histologic, and radiologic signs of type II collagen-induced arthritis.

OBJECTIVE: Human cartilage glycoprotein 39 (HC gp-39) was recently identified as a candidate autoantigen in the pathogenesis of rheumatoid arthritis. In the present studies, we investigated the capacity of HC gp-39 to interfere in clinical disease induced by an unrelated autoantigen, type II collagen (CII), by the induction of cross-tolerance. METHODS: DBA-1j/Bom mice were immunized with bovine CII/complete Freund's adjuvant and were given intraperitoneal booster injections of CII on day 21. Tolerance was induced via the intranasal pathway with either the disease-inducing antigen (CII), a control antigen (ovalbumin), or HC gp-39 either before priming with CII or near the day of the booster injection. Arthritis was monitored visually, and joint pathology was examined histologically and radiologically. In addition, CII antibody levels in serum were analyzed by enzyme-linked immunosorbent assay. RESULTS: In contrast to treatment before priming, intranasal application of HC gp-39 after immunization markedly suppressed disease activity and prevented joint destruction, whereas application of ovalbumin or CII was ineffective. Interference of HC gp-39 with the immune response to CII was demonstrated by decreased anti-CII antibody levels. The combined data indicate that intranasal treatment with HC gp-39 may trigger modulatory or regulatory mechanisms that interfere with the expression of disease in murine collagen-induced arthritis. CONCLUSION: HC gp-39 is the first cross-tolerance-inducing protein in arthritis that down-modulates a spectrum of disease features when given in a semitherapeutic protocol.

Adipokines↗

PubMed1998

Intranasal administration of HIV-DNA vaccine formulated with a polymer, carboxymethylcellulose, augments mucosal antibody production and cell-mediated immune response.

We previously reported that intramuscular (i.m.) immunization of DNA vaccine encoding human immunodeficiency virus type 1 (HIV-1)IIIB env and rev genes alone or in combination with appropriate adjuvant induces substantial and enhanced immune response against HIV-1. In the present study, we examined whether a polymer, low-viscosity carboxymethylcellulose sodium salt (CMCS-L), has an adjuvant effect on immune response induced by DNA vaccination. BALB/c mice were immunized with HIV-DNA vaccine formulated with CMCS-L via the intranasal (i.n.) and i.m. routes. The combination with the polymer elicited higher levels of antigen-specific serum IgG and fecal IgA antibodies than DNA vaccine alone. For cell-mediated immunity, HIV-specific delayed-type hypersensitivity response and cytotoxic T lymphocyte activity were measured by the footpad-swelling test and the 51Cr-release assay, respectively. Both were enhanced by the combination with CMCS-L via i.n. and i.m. inoculation. Cytokine analysis in culture media of bulk splenocytes harvested from immunized animals showed higher levels of IL-4 production in i.n. -immunized mice compared with i.m.-immunized mice. Nevertheless, the increased IFN-gamma production resulting from the combination with CMCS-L was observed only in i.n.-immunized mice. These data indicate that i.n. immunization of HIV-DNA vaccine formulated with CMCS-L enhances HIV-specific mucosal antibody (Ab) and systemic Ab and cell-mediated immune response.

AIDS Vaccines↗

PubMed1991

Mucosal and systemic antibody formation in the rat after intranasal administration of three different antigens.

In order to study the role of nasal-associated lymphoid tissue (NALT) in the local nasal immune response, rats were immunized intra-nasally with either of the following trinitrophenylated (TNP) antigens; the thymus-dependent keyhole limpet haemocyanin (KLH), or the thymus-independent lipopolysaccharide (LPS), or with the particulate (thymus-dependent) sheep red blood cells (SRBC). Primary responses hardly occurred, while only TNP-KLH elicited a considerable secondary response. The major responding organ was the posterior cervical lymph node. Specific antibody-forming cells (AFC) occurred in the medulla and were mainly of the IgA or IgG isotype. Hardly any specific AFC were found in NALT or the surrounding mucosa. Intranasal immunization evoked no antibody response in the lung. Ample anti-TNP antibodies could be detected in the sera of animals, primed and boosted with TNP-KLH or TNP-LPS. No specific serum antibodies occurred after immunization with TNP-SRBC. The results are discussed in view of the immunological defence in the upper respiratory tract.

Administration, Intranasal↗

PubMed1997

Increased neostriatal dopamine activity after intraperitoneal or intranasal administration of L-DOPA: on the role of benserazide pretreatment.

L-DOPA provides the most potent medication to treat Parkinson's disease, and such systemic treatment is usually combined with a peripheral amino acid decarboxylase inhibitor to amplify its central effectiveness. Since L-DOPA can lose its efficacy or can lead to adverse effects with prolonged application, current pharmacokinetic and dynamic research is aimed at improving the drug's applicability. In a previous study, performed with in vivo microdialysis in the anesthetized rat, we have shown that intranasal L-DOPA administration (without prior decarboxylase inhibition) can increase extracellular dopamine levels in the neostriatum. Using similar experimental conditions in the present experiment, we tested the neurochemical effects of L-DOPA treatment in combination with the peripheral amino acid decarboxylase inhibitor benserazide. In accordance with other data, it was found that the combination of i.p. benserazide and i.p. L-DOPA led to pronounced increases of extracellular levels of dopamine, dihydroxyplenylacetic acid and homovanillic acid in the neostriatum, whereas i.p. L-DOPA alone only moderately increased dopamine, but strongly increased the metabolite levels. Furthermore, increased dopamine levels, and weaker increases of dihydroxyplenylacetic acid and homovanillic acid were observed after i.p. benserazide followed by intranasal L-DOPA. Finally, we found that i.p. benserazide alone can lead to pronounced increases in neostriatal dopamine and moderate increases of dihydroxyplenylacetic acid levels, whereas it did not affect homovanillic acid. Thus, not only the combination of L-DOPA (i.p. or intranasal) with the presumed peripheral L-DOPA decarboxylase inhibitor benserazide, but also each component alone can affect dopamine activity in the brain. Especially the findings with benserazide treatment might be of relevance for understanding the mechanisms of current L-DOPA therapy, since they indicate that part of the treatment's actions may possibly be determined by central dopaminergic effects of the accompanying amino acid decarboxylase inhibitor.

Administration, Intranasal↗

PubMed1998

Intranasal administration of a meningococcal outer membrane vesicle vaccine induces persistent local mucosal antibodies and serum antibodies with strong bactericidal activity in humans.

A nasal vaccine, consisting of outer membrane vesicles (OMVs) from group B Neisseria meningitidis, was given to 12 volunteers in the form of nose drops or nasal spray four times at weekly intervals, with a fifth dose 5 months later. Each nasal dose consisted of 250 microg of protein, equivalent to 10 times the intramuscular dose that was administered twice with a 6-week interval to 11 other volunteers. All individuals given the nasal vaccine developed immunoglobulin A (IgA) antibody responses to OMVs in nasal secretions, and eight developed salivary IgA antibodies which persisted for at least 5 months. Intramuscular immunizations did not lead to antibody responses in the secretions. Modest increases in serum IgG antibodies were obtained in 5 volunteers who had been immunized intranasally, while 10 individuals responded strongly to the intramuscular vaccine. Both the serum and secretory antibody responses reached a maximum after two to three doses of the nasal vaccine, with no significant booster effect of the fifth dose. The pattern of serum antibody specificities against the different OMV components after intranasal immunizations was largely similar to that obtained with the intramuscular vaccine. Five and eight vaccinees in the nasal group developed persistent increases in serum bactericidal titers to the homologous meningococcal vaccine strain expressing low and high levels, respectively, of the outer membrane protein Opc. Our results indicate that meningococcal OMVs possess the structures necessary to initiate systemic as well as local mucosal immune responses when presented as a nasal vaccine. Although the serum antibody levels were less conspicuous than those after intramuscular vaccinations, the demonstration of substantial bactericidal activity indicates that a nonproliferating nasal vaccine might induce antibodies of high functional quality.

Administration, Intranasal↗

PubMed1999

Pharmacokinetics of zanamivir after intravenous, oral, inhaled or intranasal administration to healthy volunteers.

OBJECTIVE: The objective of these studies was to examine the clinical pharmacokinetics and safety of zanamivir, an influenza A and B virus neuraminidase inhibitor, when administered to healthy volunteers. DESIGN: The safety, tolerability and pharmacokinetics of zanamivir administered by a number of routes were assessed in randomised, double-blind and placebo-controlled studies. The study of absolute oral bioavailability had an open design. STUDY PARTICIPANTS: The participants in these studies were healthy male or female volunteers. INTERVENTIONS: Zanamivir was administered as single or multiple doses by the intravenous, oral, inhaled (nebuliser and dry powder) and intranasal routes. Serum and urine samples were obtained for determination of pharmacokinetic parameters, and nasal washes and throat gargles were performed to assess drug concentrations in the nose and throat. Safety was evaluated by monitoring adverse events, vital signs and laboratory parameters. RESULTS: Zanamivir was well tolerated at all doses by all routes; no serious adverse events were reported. The kinetics of zanamivir were linear with single intravenous doses up to 600 mg, and there was no evidence of modification in the kinetics after repeated twice-daily administration. Approximately 90% of zanamivir was excreted unchanged in the urine. The elimination of zanamivir from the serum was a first-order process with a half-life of approximately 2 hours and, at 16 L, the volume of distribution was similar to that of extracellular water. The absolute oral bioavailability of zanamivir was low, averaging 2%. After intranasal or oral inhaled administration, a median of 10 to 20% of the dose was systemically absorbed, with maximum serum concentrations generally reached within 1 to 2 hours. The median serum half-life ranged between 2.5 and 5.05 hours, suggesting that the elimination rate is limited by absorption. There was no evidence of modification in the kinetics after repeated inhaled administration. CONCLUSIONS: Zanamivir is a well tolerated drug. The low level of absorption of the drug after inhaled administration results in low serum concentrations, and therefore there is modest systemic exposure to zanamivir after inhalation. Zanamivir is not metabolised, and the potential for clinically relevant drug-drug interactions is very low.

Administration, Inhalation↗

PubMed1986

Shortening of bleeding time after intranasal administration of 1-deamino-8-D-arginine vasopressin to patients with chronic uremia.

1-deamino-8-D-arginine vasopressin (DDAVP) was administered intranasally in a dose of 2 micrograms/kg BW to 17 uremic patients (16 maintained on chronic hemodialysis and 1 treated conservatively). The bleeding time was significantly shortened 120 minutes after DDAVP administration (from 18.1 +/- 7.5 minutes to 12.3 +/- 6.4 minutes p less than 0.001). Factor VIII related antigen (VIII: Ag) did not change. Factor VIII ristocetin cofactor activity (VIII: RCof) significantly increased (from 251.2 +/- 162.0 to 336.5 +/- 167.2 p less than 0.025). Platelet count decreased significantly after DDAVP (from 174.9 +/- 43.8 X 10(9)/l to 155.6 +/- 45.9 X 10(9)/l 30 minutes p less than 0.01 and 129.8 +/- 45.2 X 10(9)/l p less than 0.005 120 minutes after DDAVP). Antithrombin III concentration, and hematocrit did not change. Our data indicate that further clinical studies of intranasal DDAVP in uremic patients during episodes of bleeding are warranted.

Administration, Intranasal↗

PubMed2001

Tissue distribution of radioactivity following intranasal administration of radioactive microspheres.

The aim of this study was to increase understanding of the kinetics of microparticle distribution and elimination following intranasal application. To do this we investigated the in-vivo distribution of radioactivity following intranasal instillation of scandium-46 labelled styrene-divinyl benzene 7-microm-diameter microspheres. Groups of BALB/c mice received 0.250 mg (47.5 kBq) particles suspended in either 50-microL or 10-microL volumes of phosphate buffered saline. The in-vivo distribution of radioactivity was influenced by the volume of liquid that was used to instil the microsphere suspension. Comparatively large (50 microL) administration vehicle volumes resulted in substantial bronchopulmonary deposition (approximately 50% of administered dose). Intranasal instillation of microspheres suspended in 10-microL volumes tended to restrict particle deposition initially to the nasal cavity. For both administration vehicle volumes tested, the radioactivity per unit mass of excised nasal-associated lymphoid tissue (NALT) was found to be consistently elevated relative to other tissues. This corroborates the findings of other workers who have previously identified NALT as an active site of microparticle accumulation following intranasal application. Elimination via the alimentary canal was the principal fate of intranasally applied radiolabelled material. No significant concentration of radioactivity within excised gut-associated lymphoid tissue (GALT) (Peyer's patches) was noted. At latter time points we observed, in mice that received the 50-microL volume particle suspension nasally, accumulation of potentially relevant quantities of radioactivity in the liver (0.3% after 576 h) and spleen (0.04% after 576 h). Thus, our data corroborate the notion that epithelial membranes in the lung are probably less exclusive to the entry of microparticulates into systemic compartments than are those mucosae in the gastrointestinal tract or nasopharynx. This effect may contribute to the effectiveness of pulmonary delivered antigen-loaded microparticles as humoral immunogens.

Administration, Intranasal↗

PubMed2001

Rapid and wide-reaching delivery of HIV-1 env DNA vaccine by intranasal administration.

Although the potential of DNA vaccination is now beginning to be greatly appreciated, no detailed study of its localization in tissue or its expression kinetics has been reported. In this study, we investigated these issues using HIV-1 DNA plasmids administered either intranasally or intramuscularly. Fluorescence in situ hybridization (FISH) revealed that the human immunodeficiency virus (HIV) plasmids administered intranasally localized in the alveoli, lung, liver, spleen, regional lymph nodes, kidney, fetus, and esophagus. These HIV plasmids were detected 2 to 4 weeks after administration. We detected messenger RNA production of HIV env gene in the lung, liver and spleen, and human immunodeficiency virus type 1 (HIV-1)-specific proteins were detectable in the lung. These observations may provide important information for understanding the mechanisms of strong immune activation induced by DNA vaccination via the intranasal route. This technology of DNA administration suggests possible practical applications for vaccination and probably for gene therapy.

AIDS Vaccines↗

PubMed1983

Intranasal administration of human pancreatic tumor GH-releasing factor-40 stimulates GH release in normal men.

Human pancreatic tumor GH releasing factor-40 (hpGRF-40) selectively stimulates GH secretion in normal men and in some adult patients with GH deficiency. As the latter finding suggests that some children with GH deficiency may benefit from therapy with hpGRF-40 or an analogue, we investigated the effect of hpGRF-40 administered intranasally on GH release. Six normal men were given hpGRF-40 (30 ug/kg; test day) or an equivalent volume of vehicle alone (control day) at 0900 h. Immunoreactive GH was measured in serum obtained at intervals between 0800-1200 h. Mean (+/- SEM) integrated serum levels of GH (ng/ml/h) prior to and following administration of vehicle were not different (1.27 +/- 0.57 vs 0.87 +/- 0.28; p = 0.54). However, following hpGRF-40 administration, GH levels increased significantly (0.53 +/- 0.03 vs 2.88 +/- 0.75; p = 0.022). Peak levels of serum GH were detected within 30 min following hpGRF-40. Except for mild burning of the nasal mucosa reported by one subject, no side effects were noted. We conclude that, if hpGRF-40 or an analogue is shown to be useful in the treatment of some children with GH deficiency, the intranasal route of administration may be utilized and will be more acceptable for chronic therapy than intravenous, intramuscular, or subcutaneous injection.

Administration, Intranasal↗

PubMed2001

Microsphere translocation and immunopotentiation in systemic tissues following intranasal administration.

With a view to developing improved mucosal immunisation strategies, we have quantitatively investigated the uptake of fluorescent polystyrene carboxylate microspheres (1.1 microm diameter), using histology and fluorescence-activated cell sorting, following intranasal delivery to BALB/c mice. To qualify these biodistribution data, antigen specific memory and effector responses in the spleens of mice immunised nasally with Yersinia pestis V antigen loaded poly(lactide) (PLA) microspheres (1.5 microm diameter) were assessed at 4, 7 and 11 days. Irrespective of administration vehicle volume (10 or 50 microl), appreciable numbers of fluorescent microspheres were detected within nasal associated lymphoid tissues (NALT) and draining cervical lymph nodes. Nasal administration of the particles suspended in 50 microl volumes of phosphate-buffered saline (PBS) served to deposit the fluorescent microspheres throughout the respiratory tract (P<0.05). In these animals, appreciable particle uptake into the mediastinal lymph node was noted (P<0.05). Also, spleens removed from mice 10 days after fluorescent particle application contained significantly more microspheres if the suspension had been nasally instilled using a 50 microl volume (P<0.05). Appreciable memory (and effector from day 7) responses were detected in mediastinal lymph nodes removed from mice immunised nasally with 50 microl volumes of microparticulated or soluble V antigen. Immunological responses in splenic tissue removed 7 days after intranasal immunisation corroborated the thesis that the spleen can act as an inductive site following bronchopulmonary deposition of particulated antigen: upon exposure to V in vitro, splenic T-cells from mice nasally immunised with 50 microl volumes of microspheres incorporated statistically greater (P<0.05) quantities of [3H]thymidine into newly synthesised DNA than did T-cells from cohorts nasally immunised with 50 microl volumes of V in solution. Similarly, significant numbers of anti-V IgG secreting cells were only detected in spleens from mice immunised intramuscularly or nasally with microparticles. These immunological and biodistribution data support the tenet that, following an appropriate method of mucosal delivery, microparticles can translocate to tissues in the systemic compartment of the immune system and thence provoke immunological reactions therein.

Adjuvants, Immunologic↗

PubMed1986

Intranasal administration of peptides: nasal deposition, biological response, and absorption of desmopressin.

The nasal administration of desmopressin [1-(3-mercaptopropionic acid)-8-D-arginine-vasopressin] in humans was investigated. Desmopressin solutions containing 99mTc-labeled human serum albumin were administered intranasally as a spray, using two metered-dose pumps, or as drops, using a rhinyle catheter or a single-dose pipet. Images of the sites of deposition and rates of clearance were monitored quantitatively by gamma scintigraphy. Plasma levels of desmopressin were measured using a highly sensitive and specific radioimmunoassay. The biological response was determined by measuring circulating levels of F VIII, the antihemophilia factor. The sprays were deposited mainly anteriorly, from which small portions were cleared slowly into the nasal pharynx. In contrast, the drops were deposited mostly posteriorly and cleared very rapidly in large portions; some were swallowed immediately. Plasma levels showed that desmopressin was absorbed to a greater extent after administration of the spray with a 2 to 3-fold increase in the relative bioavailability compared with the drops. The biological response was clearly enhanced after spray administration and produced similar increases in F VIII activity. A linear correlation was observed between maximum plasma desmopressin levels and maximum F VIII activity. The use of an intranasal spray device can deposit well-controlled doses within the nasal cavity, which remain there sufficiently long to provide a clear enhancement in absorption and bioavailability.

Absorption↗

PubMed1987

Influence of experimental rhinitis on the gonadotropin response to intranasal administration of buserelin.

The influence of experimental rhinitis on the absorption of buserelin, measured as the serum luteinizing hormone (LH) response, has been investigated. A single dose of 200 micrograms buserelin was given to 24 healthy male volunteers after induction of experimental rhinitis with histamine and after use of a saline spray (placebo control). Except on one occasion, when the pump-spray apparently was incorrectly operated, serum LH concentration rose after buserelin. There was no difference in the LH response between histamine-induced rhinitis and saline controls. It was concluded that intranasal application of buserelin represents a reliable mode of application and that modification of the administration route or a change in the dosage schedule during naturally-occurring nasal inflammations, such as the common cold and allergic rhinitis, is unnecessary in patients undergoing chronic treatment with intranasal buserelin, e.g. for prostatic cancer, endometriosis, precocious puberty, and contraception.

Absorption↗