Effectiveness of pirotiodecane, absorption enhancer, on nasal absorption in rabbits.
The absorption enhancing effect of 1-[2-(decylthio) ethyl] azacyclopentan-2-one (Pirotiodecane), on drug permeation across rabbit nasal mucosa was studied. The nasal epithelial mucosa was isolated from rabbit nasal septum and mounted in an Ussing chamber to allow for monitoring of the membrane resistance (Rm), and the permeation of fluorescein isothiocyanate-labeled dextran (FD-4, M.W. 4,400 Da). Treatment with 0.05, 0.1, and 0.2% Pirotiodecane for 60 min decreased Rm, and increased the cumulative amount of FD-4 permeated in a concentration-dependent manner, suggesting that Pirotiodecane possesses passively a disassembly of tight junction to enable the enhanced FD-4 permeation. The remarkable increase in plasma concentration of FD-4 was also observed in intranasal co-administration with 1% Pirotiodecane in rabbits. The Rm was virtually maintained after the removal of Pirotiodecane, although recovery of Rm was not seen. On the other hand, the increase in plasma concentration of FD-4 with intranasal co-administration of 1% Pirotiodecane in rabbits in vivo was not observed in FD-4 administration at 15-60 min after administration of 1% Pirotiodecane alone. It was concluded that Pirotiodecane possesses a relatively short absorption enhancing effect through nasal epithelial.
Otake
Hiroshi
H
Fundamental Research Laboratories, Development Assessment Center, R&D Division, Hisamitsu Pharmaceutical Co., Inc., Ibaraki, Japan. hiroshi-otake@hisamitsu.co.jp
Tomita
Mikio
M
Sugimoto
Mariko
M
Idota
Yoshihiro
Y
Okuma
Koji
K
Sakai
Michinori
M
Haga
Makoto
M
Hayashi
Masahiro
M
D000281:Administration, Intranasal; D000818:Animals; D019540:Area Under Curve; D007700:Kinetics; D009297:Nasal Mucosa / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits
D011758:Pyrroles; C075725:1-(2-(decylthio)ethyl)azacyclopentane-2-one