title: Visualization of drug translocation in the nasal cavity and pharmacokinetic analysis on nasal drug absorption using positron emission tomography in the rat.
abstract: We performed positron emission tomography (PET) using 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) to evaluate the pharmacokinetics of nasal drug absorption in the rat. The dosing solution of [(18)F]FDG was varied in volume (ranging from 5 to 25 μl) and viscosity (using 0% to 3% concentrations of hydroxypropylcellulose). We modeled the pharmacokinetic parameters regarding the nasal cavity and pharynx using mass balance equations, and evaluated the values that were obtained by fitting concentration-time profiles using WinNonlin® software. The regional nasal permeability was also estimated using the active surface area derived from the PET images. The translocation of [(18)F]FDG from the nasal cavity was visualized using PET. Analysis of the PET imaging data revealed that the pharmacokinetic parameters were independent of the dosing solution volume; however, the viscosity increased the absorption rate constant and decreased the mucociliary clearance rate constant. Nasal permeability was initially higher but subsequently decreased until the end of the study, indicating regional differences in permeability in the nasal cavity. We concluded that the visualization of drug translocation in the nasal cavity in the rat using PET enables quantitative analysis of nasal drug absorption, thereby facilitating the development of nasal formulations for human use.
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: tshingaki@riken.jp.
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Shingaki
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Katayama
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Nakaoka
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Irie
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Onoe
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okauchi
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Hayashinaka
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Tanki
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ose
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Wada
authors.affiliation: School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama 703-8516, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Furubayashi
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Kyoto Pharmaceutical University, 5 Misasaginakauchi-cho, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Sakane
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D019788:Fluorodeoxyglucose F18 / Q000032:analysis* / Q000493:pharmacokinetics*; D008297:Male; D065588:Nasal Absorption / Q000187:drug effects / Q000502:physiology*; D009296:Nasal Cavity / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: Nasal absorption; Nasopalatine; Pharmacokinetics; Positron emission tomography; Viscosity