Zavegepant is a novel gepant administered as a nasal spray approved in the United States at a 10 mg dose for the acute treatment of migraine with or without aura in adults. The cardiovascular safety of zavegepant nasal spray was assessed in both single-ascending dose (SAD) and multiple-ascending dose (MAD) studies in healthy participants. The SAD study included 72 participants (54 active/18 placebo) who received 0.1-40 mg zavegepant or placebo. The MAD study included 72 participants (56 active/16 placebo) who received 5-40 mg zavegepant or placebo for 1-14 days. Plasma zavegepant pharmacokinetics and electrocardiographic (ECG) parameters (Fridericia-corrected QT interval [QTcF], heart rate, PR interval, ventricular depolarization [QRS], T-wave morphology, and U-wave presence) were analyzed pre- and post-zavegepant administration. Using pooled data from the SAD and MAD studies, the relationship between time-matched plasma zavegepant concentrations and QTc interval was assessed using a linear mixed-effects model to evaluate the potential for QTc interval prolongation. Results showed that single and multiple doses of zavegepant had no significant impact on ECG parameters versus placebo, and there was no concentration-dependent effect on QTcF interval. The estimated slope of the plasma zavegepant concentration-QTcF model was -0.053 ms per ng/mL with a 90% confidence interval of -0.0955 to -0.0110 (p = 0.0415), which is not considered clinically meaningful. At doses up to four times the recommended daily dose, zavegepant does not prolong the QT interval to any clinically relevant extent.

OBJECTIVE: The purpose of this phase III randomized double-blinded controlled trial was to investigate the efficacy of a rose geranium in sesame oil (RG) nasal spray compared with an isotonic saline (IS) nasal spray for alleviating nasal vestibulitis symptoms among patients undergoing chemotherapy.
METHODS: Patients undergoing active chemotherapy who reported associated nasal symptoms were randomized 1:1 to receive RG or IS, administered twice daily for 2 weeks. Consenting participants completed nasal symptom questionnaires at baseline and then weekly while on treatment. The proportion of patients experiencing improvements in their nasal symptoms 2 weeks after initiating the nasal spray, using a six-point global impression of change score, was estimated within and between each randomized arm, and compared between arms, using Fisher\'s exact test. The estimated odds ratio was determined (95% confidence interval).
RESULTS: One hundred and six patients consented to this study; 43 participants in the RG arm and 41 in the IS arm were evaluable for the primary endpoint. Participants had a mean age of 57.8 years (SD 13.9). Demographic characteristics and baseline nasal symptoms were similar between arms. Of the evaluable participants who received RG, 67.4% reported improved nasal symptoms, compared with 36.6% of the participants who received IS (P = 0.009). Adverse events were sparse and did not differ between arms.
CONCLUSIONS: Rose geranium in sesame oil significantly improves nasal vestibulitis symptoms among patients undergoing chemotherapy.
BACKGROUND: NCT04620369.

Amiloride is a U.S. Food and Drug Administration-approved diuretic agent used to treat hypertension and congestive heart failure. Recent human and animal studies have suggested that amiloride may also have a role in treating anxiety through its acid-sensing ion channel antagonism. Intranasal administration of amiloride nasal spray via an extemporaneously compounded preparation has the potential for rapid delivery to the site of action to achieve therapeutic outcomes in individual patients with anxiety disorders. However, these patient-specific preparations do not have the pre-formulation characterization, including chemical stability, that conventional manufactured dosage forms have. The objective of this study was to assess the estimated chemical stability of compounded amiloride nasal spray over 6 months and 12 months utilizing accelerated degradation with high heat and the Arrhenius equation. A stability-indicating highperformance liquid chromatography analytical method was employed at appropriate intervals over a 12-month period to reveal that amiloride remained chemically stable over the period tested and by extrapolation. Physical stability and compatibility with the preservative benzyl alcohol were also confirmed via visual inspection, pH monitoring, and measurement of turbidity.

The nasal administration of therapeutic fluids and vaccines is used to treat allergic rhinitis, sinusitis, congestion, coronaviruses and even Alzheimer\'s disease. In the latter, the drug must reach the olfactory region, so it finds its way into the central nervous system. Effective administration techniques able to reach the olfactory region are challenging due to the tortuous anatomy of the nasal cavity, and are frequently evaluated in vitro using transparent anatomical models. Here, the liquid distribution inside a 3D printed human nasal cavity is quantified for model fluids resulting from the discharge of a 1-mL syringe with either a spray-generating nozzle, and a straight tip emitting a collimated fluid stream. Experiments using two model fluids with different viscosities suggest that a simple, correctly positioned straight tip attached to a syringe is able to efficiently deliver most of a therapeutic fluid in the human olfactory region in the side-laying position, avoiding the adoption of head-back and head-down positions that can be difficult for patients in the age range typical of Alzheimer\'s disease. Furthermore, we demonstrate by computer simulations that the conclusion is valid within a wide range of parameters.

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Background: Under a risk evaluation and mitigation strategy program, esketamine nasal spray CIII requires self administration at a certified treatment center. Our objective was to identify factors associated with esketamine initiation and continuation.
Methods: A retrospective observational cohort study was conducted among US adults who met treatment-resistant depression (TRD) criteria. Cases (n = 966) initiated esketamine between October 11, 2019, and February 28, 2022, and were compared to controls (n = 39,219) with TRD but no esketamine use. Outcomes included initiation, induction (8 administrations within 45 days), and interruptions (30-day treatment gap). Comorbid psychiatric conditions were identified using International Classification of Diseases, Tenth Revision, Clinical Modification, codes.
Results: Cases resided significantly closer to treatment centers (8.9 vs 20.3 miles). Compared to 0-9 miles, initiation rate decreased by 11.9%, 50.8%, 68.1%, 75.9%, and 92.8% for individuals residing 10-19, 20-29, 30-39, 40-49, and 50+ miles from a center. After adjustment, factors associated with increased likelihood of initiation were posttraumatic stress disorder, major depressive disorder with suicidal ideation, and male sex, while increasing distance, substance use disorder, Medicaid, Charlson Comorbidity Index (CCI), and older age were associated with lower likelihood. Factors associated with lower likelihood of completing induction were Medicaid, low socioeconomic status (SES), CCI, and Hispanic communities. Factors associated with increased likelihood of interruption were alcohol use disorder, distance, and minority communities, while generalized anxiety disorder and Medicaid were associated with lower likelihood.
Conclusions: Travel distance, insurance, low SES, and minority communities are potential barriers to treatment. Alternative care models may be needed to ensure adequate access to care.
J Clin Psychiatry 2024;85(2):23m15102.

BACKGROUND: Preschoolers frequently have respiratory infections (RIs), which may cause wheezing in some subjects. Type 2 polarization may favor increased susceptibility to RIs and associated wheezing. Non-pharmacological remedies are garnering increasing interest as possible add-on therapies. The present preliminary study investigated the efficacy and safety of a new multi-component nasal spray in preschoolers with frequent RIs and associated wheezing.
METHODS: Some preschoolers with these characteristics randomly took this product, containing lactoferrin, dipotassium glycyrrhizinate, carboxymethyl-beta-glucan, and vitamins C and D3 (Saflovir), two sprays per nostril twice daily for 3 months. Other children were randomly treated only with standard therapy. Outcomes included the number of RIs and wheezing episodes, use of medications, and severity of clinical manifestations.
RESULTS: Preschoolers treated add-on with this multicomponent product experienced fewer RIs and used fewer beta-2 agonists than untreated children (P = 0.01 and 0.029, respectively).
CONCLUSIONS: This preliminary study demonstrated that a multicomponent product, administered add-on as a nasal spray, could reduce the incidence of RIs and use of symptomatic drugs for relieving wheezing in children.

The studyCarrie S, O\'Hara J, Fouweather T, et al. Clinical effectiveness of septoplasty versus medical management for nasal airways obstruction: multicentre, open label, randomised controlled trial. BMJ 2023;383:e075445.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/surgery-is-better-than-nasal-sprays-for-people-with-severely-blocked-airways/.

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BACKGROUND: Little is known about rhinitis control in real-life, nor about the contribution of treatment-related and patient-related factors.
OBJECTIVE: This study aimed to examine the level of rhinitis control and rhinitis medication utilization in patients with persistent rhinitis and to identify predictors of rhinitis control.
METHODS: A cross-sectional observational study was conducted in patients with persistent rhinitis recruited in community pharmacies. Participants completed the Rhinitis Control Assessment Test, a questionnaire on patient/rhinitis characteristics, and rhinitis medication use. A visual analog scale for nasal symptoms was also completed. Pharmacy dispensing data were used to calculate adherence to intranasal glucocorticoids. Nasal spray technique was evaluated using a standardized checklist. Predictors of rhinitis control were explored using a linear regression model.
RESULTS: A total of 1,514 patients, recruited in 215 pharmacies, participated in the study (mean age 48.7 y, 62% female). Almost 60% exhibited suboptimal rhinitis control (Rhinitis Control Assessment Test ≤ 21 of 30). A 50-mm cut-off on the visual analog scale yielded 78.1% sensitivity to identify suboptimal rhinitis control. Participants most frequently used intranasal glucocorticoids (55.6%) and intranasal decongestants (47.4%). Only 10.3% of current nasal spray users demonstrated perfect technique. More than half (54.8%) of glucocorticoid users were identified as underadherent. Female sex, self-reported nasal hyperreactivity, active asthma, and use of oral/intranasal decongestants or nasal saline were identified as predictors of worse rhinitis control.
CONCLUSIONS: Suboptimal rhinitis control was common in this real-life sample of persistent rhinitis patients. Improving use of rhinitis medication may be key to increase disease control.