Pharmacokinetic Study of Intranasal Dexamethasone and Methylprednisolone Compared with Intravenous Administration: Two Open-Label, Single-Dose, Two-Period, Two-Sequence, Cross-Over Study in Healthy Volunteers

Authors

Graciela Cárdenas
Raúl J. Bobes
Gladis Fragoso
Nicolas I. Pérez-Osorio
Marisela Hernández
Alejandro Espinosa
Agnes Fleury
José Flores
Juan Carlos Alvarenga, The University of Texas Rio Grande ValleyFollow
Juan Pedro Laclette

Document Type

Article

Publication Date

12-28-2022

Abstract

Dexamethasone (DXM) and methylprednisolone (MEP) are potent glucocorticoids used to control several inflammatory conditions. Evidence of delayed DXM reaching the central nervous system (CNS) as well as tachyphylaxis and systemic, undesirable side effects are the main limitations of peripheral delivery. Intranasal administration offers direct access to the brain as it bypasses the blood–brain barrier. The Mucosal Atomization Device is an optimal tool that can achieve rapid absorption into the CNS and the bloodstream across mucosal membranes. This study was designed to evaluate and compare the bioavailability of DXM and MEP after intranasal versus intravenous administration. Two open-label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover studies were conducted, which involved healthy male and female adult volunteers. After intranasal administration, DXM and MEP were detected in plasma after the first sampling time. Mean peak concentrations of DXM and MEP were 86.61 ng/mL at 60 min and 843.2 ng/mL at 1.5 h post-administration, respectively. DXM and MEP showed high absolute bioavailability, with values of 80% and 95%, respectively. No adverse effects were observed. DXM and MEP systemic bioavailability by intranasal administration was comparable with the intravenous one, suggesting that the intranasal route can be used as a non-invasive and appropriate alternative for systemic drug delivery.

Comments

© 2022 by the authors.

Recommended Citation

Cárdenas, G.; Bobes, R.J.; Fragoso, G.; Pérez-Osorio, N.I.; Hernández, M.; Espinosa, A.; Fleury, A.; Flores, J.; The Revival Project Consortium; Laclette, J.P.; et al. Pharmacokinetic Study of Intranasal Dexamethasone and Methylprednisolone Compared with Intravenous Administration: Two Open-Label, Single-Dose, Two-Period, Two-Sequence, Cross-Over Study in Healthy Volunteers. Pharmaceutics 2023, 15, 105. https://doi.org/10.3390/ pharmaceutics15010105

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Title

Pharmaceutics

DOI

10.3390/pharmaceutics15010105

Academic Level

faculty