Left-right difference in brain pharmacokinetics following nasal administration via one-site nostrils

Akiko Tanaka; Akiko Kiriyama; Ayaka Sano; Cho Changung; Hidemasa Katsumi; Akira Yamamoto; Tomoyuki Furubayashi

doi:10.1016/j.xphs.2024.05.003

Left-right difference in brain pharmacokinetics following nasal administration via one-site nostrils

J Pharm Sci. 2024 May 9:S0022-3549(24)00174-6. doi: 10.1016/j.xphs.2024.05.003. Online ahead of print.

Authors

Akiko Tanaka¹, Akiko Kiriyama², Ayaka Sano³, Cho Changung³, Hidemasa Katsumi⁴, Akira Yamamoto⁴, Tomoyuki Furubayashi³

Affiliations

¹ Laboratory of Pharmaceutical Technology, Kobe Pharmaceutical University, Motoyamakita-machi 4-19-1, Higashinada, Kobe, 658-8558, Japan. Electronic address: a-tanaka@kobepharma-u.ac.jp.
² Department of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto, 610-0395, Japan.
³ Laboratory of Pharmaceutical Technology, Kobe Pharmaceutical University, Motoyamakita-machi 4-19-1, Higashinada, Kobe, 658-8558, Japan.
⁴ Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina, Kyoto, 607-8414, Japan.

PMID: 38734208
DOI: 10.1016/j.xphs.2024.05.003

Abstract

The olfactory and trigeminal pathways are direct delivery pathways between the nose and brain. To determine the effect of direct delivery on drug distribution in the brain, two model drugs with different physical properties, antipyrine (ANP), with high membrane permeability, and ranitidine (RNT), with low membrane permeability, were selected. For ANP, direct delivery from the nose to the brain was observed only in the olfactory bulb beside the nasal cavity, with a direct transport percentage (DTP) of approximately 45%, whereas in the frontal and occipital brains, the contribution from the systemic circulation to the brain was observed as the primary route of brain distribution. No significant variations were observed in the pharmacokinetics of ANP in the left and right brain, whereas RNT was distributed in all brain regions with a DTP of > 95%. The closer the brain region is to the nasal cavity, the higher the DTP. Furthermore, the left brain, the same nostril site (left nostril) of administration, had a larger level of drug delivery than the right brain. These findings imply that the influence of the administered nostril site differs based on the physicochemical properties and amount of the drug.

Keywords: Nose to brain; brain delivery; brain pharmacokinetics; nasal administration.