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Comparison of intravenous and intranasal administration of epinephrine during CPR in a canine model.

STUDY OBJECTIVES: Epinephrine improves coronary perfusion pressure during CPR. However, administration of epinephrine during CPR may be delayed or omitted if IV or endotracheal access is not established. Therefore, the objective of this study was to determine if intranasal administration of epinephrine during CPR would provide an alternate route of drug administration that is readily accessible and requires no special technical skills. DESIGN AND SETTING: Randomized blinded study performed in a controlled laboratory environment. TYPE OF PARTICIPANTS: Twenty mongrel dogs weighing 19.5 +/- 4.6 kg. INTERVENTIONS: All dogs received either IV epinephrine 0.015 mg/kg or intranasal epinephrine 14 mg per nostril. Phentolamine (5 mg per nostril) was administered intranasally one minute before nasal administration of epinephrine to improve absorption. Each dog underwent three minutes of ventricular fibrillation followed by seven minutes of CPR with a pneumatic chest compression device. Epinephrine was administered at two minutes into CPR. MEASUREMENTS AND MAIN RESULTS: Seven dogs were excluded because of inadequate baseline coronary perfusion pressure or compression device displacement, leaving a total of 13 dogs for analysis (six IV epinephrine, seven intranasal epinephrine). Baseline coronary perfusion pressure (mean +/- SD) was similar for IV epinephrine and intranasal epinephrine (16.9 +/- 7.1 mm Hg versus 18.2 +/- 13.8 mm Hg, respectively, P = .84). For IV and intranasal epinephrine, coronary perfusion pressure increased to 21.4 +/- 9.2 mm Hg and 24.4 +/- 18.7 mm Hg one minute after epinephrine, respectively (P = .73). Five minutes after epinephrine coronary perfusion pressure was 18.2 +/- 8.7 mm Hg and 24.3 +/- 13.9 mm Hg for IV epinephrine and intranasal epinephrine, respectively (P = .38). The rate of successful resuscitation was similar for both groups, five of seven dogs for intranasal epinephrine and four of six dogs for IV epinephrine (P = .66). CONCLUSION: Intranasal epinephrine has similar effects on coronary perfusion pressure and resuscitation compared with standard-dose IV epinephrine. Therefore, the nasal route for administration of epinephrine appears to be an acceptable alternate method of drug delivery during CPR and compares favorably with standard IV therapy in the canine model. Because of the obvious benefits to human patients, these observations suggest further investigation.

Administration, Intranasal↗

Cerebral neurogenesis is induced by intranasal administration of growth factors.

Neurogenesis persists in the adult brain, where it may contribute to repair and recovery after injury, but the lack of methods for noninvasive stimulation of cerebral neurogenesis limits its potential for clinical application. We report that intranasal administration of either fibroblast growth factor-2 or heparin-binding epidermal growth factor-like growth factor increases neurogenesis, measured by the incorporation of bromodeoxyuridine into cells that express the early neuronal marker protein doublecortin in the subventricular zone of mouse brain. These findings indicate that intranasal growth factors may have potential as neurogenesis-promoting therapeutic agents.

Administration, Intranasal↗

Effect of absorption promoters in intranasal administration of human fibroblast interferon as a powder dosage form in rabbits.

The utility of the absorption promoters, sodium glycocholate (GC-Na), ethylenediamine dihydrochloride (EDTA-2Na), sodium caprylate (Cap-Na) and sodium salicylate (Sal-Na), in the intranasal administration of human fibroblast interferon-beta (HuIFN-beta) in rabbits was investigated. The optimal amount of added EDTA-2Na, Cap-Na and Sal-Na with respect to HuIFN-beta was examined for nasal absorption in the powder dosage form. Formulations of HuIFN-beta with GC-Na showed greatly enhanced intranasal HuIFN-beta absorption, as compared to the other absorption promoters. The results of a stability study on HuIFN-beta in homogenates of nasal mucosa suggested that GC-Na behaved as a hydrolysis inhibitor in the nasal mucosa and maintained the activity of HuIFN-beta.

Absorption↗

Intranasal administration of recombinant human cartilage glycoprotein-39. A phase I escalating cohort study in patients with rheumatoid arthritis.

OBJECTIVE: To investigate safety and tolerability and pilot efficacy of repeated single doses of Org39141 in patients with active rheumatoid arthritis (RA). Org 39141 is recombinant human cartilage glycoprotein-39, intended to induce mucosal tolerance upon intranasal administration. METHODS: RA patients with moderate disease activity were treated for 4 weeks and followed for another 8 weeks. The trial had a sequential cohort design: RA patients in the first cohort received 4 intranasal doses (one per week) of either 25 microg Org 39141 or placebo; in subsequent cohorts, treatment with 125microg, 625 microg, or 3125 microg Org39141 was compared to placebo. Safety was evaluated by means of reporting adverse events, standard laboratory testing, and nose examination. The primary efficacy endpoint was RA disease activity as measured by the Disease Activity Score 28 (DAS28). RESULTS: A total of 36 patients were randomized. Org39141 was well tolerated, and no severe or serious adverse events (AE) were reported. In the pooled placebo group, a decrease in DAS28 was observed, but to a lesser extent than in the Org 39141 treatment groups. After 4 weeks of treatment, the mean decrease in DAS in the 625 microg Org 39141 treatment group (-24%) was statistically (p = 0.02) and clinically (EULAR criteria) significantly larger than in the pooled placebo group (-3%). Once-weekly intranasal treatment with Org39141 was well tolerated, and no serious or severe AE were reported. A trend towards efficacy was observed. Our results are encouraging for further clinical development of Org39141.

Adipokines↗

Estimation of bioavailability of salmon calcitonin from the hypocalcemic effect in rats (II): effect of protease inhibitor on the pharmacokinetic-pharmacodynamic relationship after intranasal administration.

Assessment of the extent of bioavailability (EBA) of salmon calcitonin (sCT) from hypocalcemic effects after intranasal administration was presented in rats. An integrated pharmacokinetic-pharmacodynamic (PK-PD) model with the endogenous Ca regulation system was applied. The influence of camostat mesilate, a protease inhibitor, on absorption of sCT was also estimated. Camostat, coadministered intravascularly, delayed the elimination of sCT. Although the hypocalcemic effect of sCT after i.v. administration was accelerated when camostat was coadministered intravenously, the enhanced effect could not be expressed only by pharmacokinetic change of sCT, and then the pharmacological data in the presence of camostat were analyzed to obtain optimal PD parameters. For the absorption of sCT after i.n. administration, a saturable absorptive process and a zero-order kinetic clearance from the nasal cavity were introduced to the model. The regression curves fitted the observed data, and camostat caused both an increase in maximum absorption rate and a decrease in the clearance parameter compared with the control. According to this modified PK-PD relationship, plasma sCT concentrations following i.n. administration of sCT with camostat were predicted well using its pharmacological effects. The EBA of sCT calculated from the simulated concentrations increased more than 4-folds compared with the control study. These results indicate the potential for prediction of plasma sCT concentration from the hypocalcemic effect.

Journal Article↗

Enhanced immunoprotective potential of Mycobacterium tuberculosis Ag85 complex protein based vaccine against airway Mycobacterium tuberculosis challenge following intranasal administration.

This study examined the role of intranasal vaccination with Mycobacterium tuberculosis antigen85 complex proteins formulated in dimethyldioctadecylammonium bromide against airway Mycobacterium tuberculosis challenge in mice. Intranasal vaccination with antigen85A and antigen85B induced a significantly higher level of interferon-gamma, interleukin-12 and interleukin-4 in cervical lymph nodes together with IgA and IgG, predominantly IgG2a isotype in nasal secretion over subcutaneous vaccination. Further, intranasal vaccination with antigen85A and antigen85B imparted protection comparable with that obtained from intranasal or subcutaneous Mycobacterium bovis bacillus Calmette-Guerin immunization. These results suggest that mucosal vaccination via the intranasal route is of importance in the development of vaccine for tuberculosis.

Acyltransferases↗

Estimation of absorption rate of alpha-human atrial natriuretic peptide from the plasma profile and diuretic effect after intranasal administration to rats.

The absorption rate of alpha-human atrial natriuretic peptide (alpha-hANP) after intranasal (i.n.) administration to rats was estimated from the plasma profile and pharmacological effect (diuretic effect) using a pharmacokinetic (PK) model and a PK-pharmacodynamic (PD) model involving data obtained after intravenous (i.v.) bolus injection. The plasma concentrations of alpha-hANP after i.v. administration at different doses were fitted to a two-compartment PK model with zero-order excretion and input of endogenous alpha-rat atrial natriuretic peptide (alpha-rANP) and two elimination processes represented by Michaelis-Menten and first-order kinetics. However, the saturable process was ignored at low doses. The plasma concentrations after low doses via the i.n. route could also be expressed by this model, but with first-order absorption, so that an absorption rate constant was calculated using a deconvolution method. In addition, the diuretic effect plotted against the i.v. dose was represented by the Hill equation and showed an anti-clockwise hysteresis loop versus the plasma concentration. These results suggest that the diuretic effect could be estimated by a PK-PD model having an 'effect' compartment or a homeostatic system. Such a PK-PD model accurately expressed the diuretic effect of alpha-hANP at all doses after i.v. and i.n. administrations. The resulting absorption rate constant calculated using the PK-PD model agreed closely with that obtained by the PK model alone. The absorption rate and simulated diuretic effect suggest that, for i.n. administration of alpha-hANP, a higher absorption rate constant causes a more potent diuretic effect (a dramatic effect over the early period), whereas greater bioavailability is associated with a better hypotensive effect (sustained effect).

Absorption↗

Hyposensitization to allergic reaction in rDer f 2-sensitized mice by the intranasal administration of a mutant of rDer f 2, C8/119S.

C8/119S is a mutant of recombinant Der f 2 (rDer f 2), and lacks a disulphide bond possessed by wild-type rDer f 2. In humans and mice, C8/119S has a very weak IgE-binding capacity compared with the wild-type, but possesses a T cell reactivity comparable to that of the wild-type. C8/119S may thus be a safe immunotherapeutic agent for house dust mite allergy. The aim of the present study was to evaluate whether the intranasal administration of C8/119S could suppress an immediate allergic reaction in mice sensitized with wild-type rDer f 2, possessing an allergic activity comparable to native counterparts purified from mite extract. Seven-week-old male A/J mice were immunized with wild-type rDer f 2 four times, and then intranasally administered 0.2-2 microg of wild-type, 0.2-20 microg of C8/119S, or PBS alone, three times a week for 4 weeks. Seven days after the last administration, the mice were examined for an immediate allergic reaction. The animals administered 2 microg of C8/119S (C2.0 group) showed significantly reduced immediate bronchoconstriction provoked by the i.v. injection of 1 and 10 microg of wild-type rDer f 2, compared with the PBS-treated mice. Similar results were obtained when we examined mice 10 weeks after the last administration. The reactions in the other groups given wild-type or C8/119S also tended to decrease in severity in comparison with the animals of the PBS group. The allergic phenotypes of the T cells, B cells, and basophils in the C2.0 group were shifted to that of naive mice without immunization. We conclude that C8/119S has hyposensitizing activities in mice sensitized with wild-type rDer f 2. C8/119S may be useful for immunotherapy of house dust mite allergy.

Administration, Intranasal↗

Intranasal administration of eotaxin increases nasal eosinophils and nitric oxide in patients with allergic rhinitis.

BACKGROUND: Nitric oxide (NO) plays an important role as an inflammatory mediator in the airways. Inducible NO synthase in the nasal mucosa is upregulated in perennial allergic rhinitis, and nasal NO is reduced after treatment with topical corticosteroids. A previous study has suggested that there is a significant correlation between exhaled NO and sputum eosinophils in patients with asthma. OBJECTIVE: We investigated the ability of intranasal administration of eotaxin, a potent chemoattractant for eosinophils, to induce eosinophil accumulation and the relationship between eosinophil recruitment in the nasal mucosa and nasal NO production in patients with allergic rhinitis. METHODS: Nine patients with allergic rhinitis were studied. Eotaxin or diluent was delivered intranasally in patients by using a metered spray pump. Nasal NO, symptom scores, and the influx of inflammatory cells in nasal lavage fluid were assessed before and after the challenge. Immunoreactivity for inducible NO synthase and nitrotyrosine was evaluated in nasal lavage cells. RESULTS: Eotaxin induced a significant influx of eosinophils (P <.05) with mild symptoms of rhinitis. There was neither significant migration of lymphocytes, basophils, and macrophages into nasal lavage fluid nor a shedding of nasal epithelial cells after eotaxin challenge. Nasal NO was increased significantly (P <.05) 8 hours after eotaxin challenge compared with diluent challenge. Nitrotyrosine immunoreactivity was moderately elevated in nasal epithelial cells after the challenge. CONCLUSION: We have shown that eotaxin causes chemotaxis of eosinophils with a clinically symptomatic inflammatory response in the nasal mucosa and that eosinophil recruitment accompanies an increase in nasal NO, contributing to oxidative stress.

Administration, Intranasal↗

Intranasal administration of one alpha gliadin can downregulate the immune response to whole gliadin in mice.

The mucosal lesion present in coeliac disease is an immune-mediated injury triggered by gliadin and restricted by a particular assortment of major histocompatibility complex genes. In view of this, an immunomodulatory approach that induces tolerance to this antigen appears to be a possible alternative to a strict gluten-free diet in treating coeliac disease. We have shown that intranasal administration of multiple doses of whole gliadin is required to specifically inhibit T helper 1-like T-cell reactivity in BALB/c mice immunized parenterally with whole gliadin. However, T-cell activation to multiple antigens, as a consequence of the chemical complexity shown by the antigen gliadin, could hamper efforts to identify single component(s) useful for tolerance induction. In this study, gliadin fractions were purified and administered intranasally to study their ability to induce tolerance to whole gliadin in our animal model. We found that the alpha fraction was particularly effective in downregulating both the in vitro gliadin-specific T-cell proliferation and interferon-gamma production to whole gliadin. In particular, a purified alpha-gliadin was able to suppress the immune response to the entire gliadin mixture. These results demonstrate how an immune response to a complex antigen may be controlled by treatment with a purified component and specifically indicate alpha-gliadin to be a good candidate for further identification of short peptides to be used as tolerogens in this model.

Administration, Intranasal↗

The risk is in the air: Intranasal administration of MPTP to rats reproducing clinical features of Parkinson's disease.

Many studies have shown that deficits in olfactory and cognitive functions precede the classical motor symptoms seen in Parkinson's disease (PD) and that olfactory testing may contribute to the early diagnosis of this disorder. Although the primary cause of PD is still unknown, epidemiological studies have revealed that its incidence is increased in consequence of exposure to certain environmental toxins. In the present study, we demonstrated that rats treated with intranasal infusion of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at low concentrations (0.1 mg/nostril) suffered progressive impairments in olfactory, cognitive and motor functions that were assessed with the olfactory discrimination, Morris water maze and open field tests, respectively. Moreover, intranasal administration of MPTP reduced the expression of the enzyme tyrosine hydroxylase in the olfactory bulb and substantia nigra of rats, resulting in a significant reduction of dopamine concentration in the olfactory bulb, prefrontal cortex and striatum, but not in the hippocampus. These results reinforce the notion that the olfactory system represents a particularly sensitive route for the transport of neurotoxins into the central nervous system that may be related to the etiology of PD. In addition, the time course of the olfactory, cognitive and motor impairments verified in rats treated intranasally with MPTP, which appears to be correlated with different stages of the human PD, suggest that the MPTP intranasal model in rats may provide new insights into the underlying mechanisms of PD pathogenesis.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Intranasal administration of insulin with phospholipid as absorption enhancer: pharmacokinetics in normal subjects.

The pharmacokinetics of intranasal insulin containing a medium-chain phospholipid (didecanoyl-L-alpha-phosphatidylcholine) as absorption enhancer, was studied in normal volunteers by measuring plasma glucose, insulin, C-peptide, and glucagon. Eleven fasting subjects received 4 U insulin intravenously, 6 U subcutaneously, or three doses intranasally (approximately 0.3 U kg-1, 0.6 U kg-1, 0.8 U kg-1) in random order on five separate days. Intranasal insulin was absorbed in a dose-dependent manner with a mean plasma insulin peak 23 +/- 7 (+/- SE) min after administration. Mean plasma glucose nadir was seen after 44 +/- 6 min, 20 min later than following intravenous injection. Furthermore, intranasal administration of insulin resulted in a faster time-course of absorption than subcutaneous injection, with significantly reduced intersubject variation (p less than 0.001). Bioavailability for the nasal formulation was 8.3% relative to an intravenous bolus injection when plasma insulin was corrected for endogenous insulin production estimated by C-peptide. A dose-dependent suppression of C-peptide and stimulation of glucagon secretion occurred after intranasal administration of insulin. Nasal irritation from spraying was absent or slight.

Absorption↗

Efficacy of intravaginal and intranasal administration of micronized estradiol-17beta.

Absorption of micronized 17beta-estradiol (E2), after intravaginal administration of 1 mg dose, suspended in saline, is extremely rapid and sustained. A mean peak increment of circulating E2 concentrations of more than 110 times the basal level is achieved at 2 h and remains elevated more than 6 times the basal level even at 24 h. Increments in estrone (E1) are smaller and slower than those of E2 with a mean peak concentration of less than 10% of E2 and remain 3 times the basal level at 24 h. With 0.5 mg dose, the incremental changes in E2 and E1 as well as the degree of gonadotropin suppression are essentially the same. In contrast, intranasal administration of E2 of 1 mg dose induces a rapid but short-lasting increase in both serum E2 and E1 levels. The mean increments of E1 exhibited a higher and sustained elevation with a rise in mean E1/E2 ratio well above unity beginning 1 hr after intranasal application. These findings indicate intravaginal but not intranasal routes of E2 absorption are quantitatively much greater and circumvent the local conversion of E2 to E1 observed after oral administration of E2, and thus represent a practical and highly effective means of delivering E2 into the circulation.

Administration, Intranasal↗

Ketamine as an analgesic: parenteral, oral, rectal, subcutaneous, transdermal and intranasal administration.

Ketamine is a parenteral anesthetic agent that provides analgesic activity at sub-anesthetic doses. It is an N-methyl-D-aspartate (NMDA) receptor antagonist with opioid receptor activity. Controlled studies and case reports on ketamine demonstrate efficacy in neuropathic and nociceptive pain. Because ketamine is a phencyclidine analogue, it has some of the psychological adverse effects found with that hallucinogen, especially in adults. Therefore, ketamine is not routinely used as an anesthetic in adult patients. It is a frequently used veterinary anesthetic, and is used more frequently in children than in adults. The psychotomimetic effects have prompted the DEA to classify ketamine as a Schedule III Controlled Substance. A review of the literature documents the analgesic use of ketamine by anesthesiologists and pain specialists in patients who have been refractory to standard analgesic medication regimens. Most reports demonstrate no or mild psychotomimetic effects when ketamine is dosed at sub-anesthetic doses. Patients who respond to ketamine tend to demonstrate dramatic pain relief that obviates the desire to stop treatment due to psychotomimetic effects (including hallucinations and extracorporeal experiences). Ketamine is approved by the FDA for intravenous and intramuscular administration. Use of this drug by the oral, intranasal, transdermal, rectal, and subcutaneous routes has been reported with analgesic efficacy in treating nociceptive and neuropathic pain. Ketamine also has been reported to produce opioid dose sparing and good patient acceptance. A transdermal formulation is currently under patent review in Brazil and an intranasal formulation is currently undergoing phase I/II clinical trials.

Administration, Cutaneous↗

[Treatment of prostatic cancer with intranasal administration of LHRH analog, Buserelin (Hoe 766) study of the optimum dosage of intranasal application].

Patients with pathologically defined prostatic carcinoma (114 cases in 23 institutes) were subcutaneously administered 500 micrograms of Buserelin (Hoe 766) 3 times a day for 7 consecutive days, then randomized to intranasally administered 600 or 900 micrograms/day of Buserelin as maintenance treatment. We examined the clinical efficacy, safety and endocrinological effects of the drug by the intranasal dosage. Size of prostate decreased more than 25% in 21 cases (total 47 cases; measured at the start and 3 months treatment by ultrasonography. Complete response and partial response were observed in 13 cases (16.1%) by NPCP's criteria at 3 months Buserelin treatment. Grobal Improvement Rating (GIR) were respectively 64.3% (600 micrograms group) and 68.0% (900 micrograms group). Grobal Utility Rating (GUR) were respectively 85.7% (600 micrograms group) and 82.0% (900 micrograms group). No significance was observed in these two groups. Adverse reactions were observed in 21 cases (18.9%). Except in 1 case, they were slight and the Buserelin treatment could be continued. Objectively Safety Rating (OSR) was 92.8%. Five cases were treated for more than 2 years with Buserelin and these cases were well controlled. Buserelin was considered as an effective and safe drug to treat prostatic carcinoma.

Administration, Intranasal↗

An ultrastructural examination of murine alveolar macrophages following intranasal administration of propionibacterium acnes.

Light and electron microscopic analysis of murine lungs or isolated pulmonary cells was performed three days after intranasal administration of the bacterial immunostimulant, Propionibacterium acnes (P. acnes). Our observations indicated that pulmonary alveolar and airway macrophages (PAMs) were the only cells with P. acnes bacilli in their cytoplasm. Bacilli were not observed in pulmonary interstitial macrophages, granulocytes, lymphocytes or pulmonary parenchymal cells such as type I and type II pneumocytes. Because of the morphological heterogeneity of PAMs observed in control and experimental animals, it was not possible from these studies to be certain about the relative abundance or complexity of lysosomes, endoplasmic reticulum, Golgi and other organelles in the two groups. However, we noted that it was not uncommon to observe in the same PAM, profiles of P. acnes and a well developed Golgi complex and endoplasmic reticulum. These P. acnes--associated morphological alterations occurred at a time when functional activities (e.g., phagocytosis, cytostasis) of PAMs were enhanced.

Animals↗

Increase in total blood leukocyte count following intranasal administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rabbits with cyclophosphamide-induced leukopenia.

We investigated the effects of intranasal (i.n.) administration of recombinant human granulocyte colony-stimulating factors (rhG-CSF) on the total count of leukocytes in peripheral blood (total blood leukocyte count) of rabbits with leukopenia who received cyclophosphamide (CPA). When CPA (30 mg/kg per d) was administered intravenously, the total blood leukocyte count decreased to levels below 5000/microliters approximately 4 d after the initiation of CPA multiple dosing. The decreased level of the total blood leukocyte count was maintained throughout the period of CPA dosing. RhG-CSF was given once a day for 3 d in CPA-treated rabbits via i.n. administration of aqueous preparations containing rhG-CSF with or without alpha-cyclodextrin (alpha-CyD). The total blood leukocyte count increased from levels below 5000/microliters to the normal physiological level following i.n. administration of rhG-CSF preparation and reduced the period of leukopenia induced by CPA. The coadministration of rhG-CSF and alpha-CyD was more effective in increasing the total blood leukocyte count. It is suggested that i.n. administration of rhG-CSF is promising for reducing the risk of cytotoxic chemotherapy (CPA)-induced leukopenia as an adverse side effect.

Administration, Intranasal↗

Intranasal administration of adrenocorticotropin-(1-24) stimulates adrenocortical hormone secretion.

To determine the efficiency of transmucosal absorption of ACTH, we measured serum cortisol, aldosterone, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S) levels after intranasal (in) vs. iv administration of ACTH-(1-24) (250 microg) in 12 healthy adult men (mean age, 24.3 +/- 3.2 yr; range, 21-31 yr), who had received no prior medication and had no symptoms of rhinitis. Blood was collected at 0, 30, 60, 120, and 180 min after administration of ACTH-(1-24), and the levels of adrenocortical steroids were measured by specific RIAs. There were no side-effects associated with in or iv ACTH administration. After in administration, serum cortisol and aldosterone increased rapidly by 224.7 +/- 39.2% and 147.2 +/- 50.5%, respectively, peaking 30 min after ACTH-(1-24) administration, and decreasing to basal levels within 120 min. These increases in serum cortisol and aldosterone were lower than those obtained after iv administration. Thirty minutes after in or iv administration of ACTH-(1-24), DHEA increased by 49.1 +/- 27.2% and 81.6 +/- 17.1%, respectively, and remained elevated for 180 min. Serum DHEA-S levels did not change after in administration of ACTH-(1-24) and increased only slightly after iv injection. Adrenocortical steroid levels did not increase after in administration of saline. These data demonstrate that adrenocortical steroids are stimulated by in administration of ACTH-(1-24). We suggest that intranasal administration of ACTH offers both a diagnostic approach as an adrenal function test and a therapeutic approach as ACTH replacement therapy in patients with ACTH deficiency. The latter may be more physiological than glucocorticoid replacement.

Administration, Intranasal↗