Optimizing Absorption for Intranasal Delivery of Drugs Targeting the Central Nervous System Using Alkylsaccharide Permeation Enhancers

Madden, Stephen F.; Carrazana, Enrique; Rabinowicz, Adrián L.

doi:10.3390/pharmaceutics15082119

Cited by 5 publications

(1 citation statement)

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“…Exposure to a hypercapnic gas mixture has a drying effect on the nasal mucosa (Lynn Webster, personal observation) which may have blunted the effect of the nasal absorption enhancer, dodecylmaltoside (DDM), included in this formulation. 12 DDM increases the absorption of both small molecules and peptides by transiently opening tight junctions between cells in the nasal epithelium 34,35 and has been demonstrated to both increase the C max and dramatically reduce the T max of nalmefene. 36 Consistent with this hypothesis, the most prominent differences in the pharmacokinetic properties of nasal nalmefene between previous studies in healthy volunteers 12 and the current study were observed during the first 20 min post administration, while plasma concentrations at 60 and 120 min were similar (Table 3).…”

Section: Discussionmentioning

confidence: 99%

Reversal of Opioid‐Induced Respiratory Depression in Healthy Volunteers: Comparison of Intranasal Nalmefene and Intranasal Naloxone

Ellison,

Hutton,

Webster

et al. 2024

The Journal of Clinical Pharma

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An open‐label, randomized, crossover study in healthy volunteers compared the reversal of remifentanil‐induced respiratory depression by intranasal (IN) naloxone hydrochloride (4 mg) to IN nalmefene (2.7 mg) (NCT 04828005). Subjects were administered a hypercapnic gas mixture which produces an elevation in minute ventilation (MV), a result of the ventilatory response to hypercapnia. Subjects breathed a hypercapnic gas mixture through a tight‐fitting mask for an initial period of 46 min prior to a series of mask “holidays” introduced to reduce subject discomfort and encourage study completion. Ten minutes after initiating the hypercapnic gas mixture, a remifentanil bolus was administered, and an infusion continued for the study duration. Subjects were administered either naloxone or nalmefene 15 min after initiating the remifentanil infusion and MV monitored for 21 min followed by a mask holiday. Both nalmefene and naloxone produced a time‐dependent reversal of remifentanil‐induced reductions in MV measured 2.5–20 min post administration. At the primary endpoint (5 min post administration), nalmefene increases in MV (5.75 L/min) were nearly twice that produced by naloxone (3.01 L/min) (P < .0009); the point estimate favors nalmefene, demonstrating non‐inferiority and superiority. In this model of opioid‐induced respiratory depression, nalmefene has a more rapid onset of action than naloxone, which required 20 min to achieve a comparable reversal of respiratory depression. Both nalmefene and naloxone were well tolerated by healthy volunteers. This rapid onset of action may prove particularly valuable in an era when over 90% of fatalities are linked to synthetic opioid overdose.

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Section: Discussionmentioning

confidence: 99%