Estimation of in vivo percutaneous absorption of emedastine from bile excretion data using a deconvolution method.
In vivo percutaneous absorption of emedastine difumarate was investigated in rats and compared with rat skin in vitro. Since emedastine entering the systemic circulation is mostly excreted in bile, we first came up with the method of collecting bile with a minimal skin incision. In vivo skin permeation of the drug was estimated from biliary excretion data by deconvolution analysis. Prior to applying deconvolution analysis, it was confirmed that biliary excretion of emedastine was linear against its dose. When the in vivo permeation profile estimated by deconvolution was compared with the in vitro profile, the lag time for permeation was significantly shorter in vivo than in vitro, whereas the skin permeability coefficient was almost the same. If we presume a two-layer diffusion model, then this finding may primarily be due to the shorter diffusion length of the dermis.
Harada
Shoichi
S
Clinical Project Management, Nippon Organon K.K., Dojima, Osaka, Japan. shoichi.harada@organon.jp
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000279:Administration, Cutaneous; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004058:Diffusion; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption
D001562:Benzimidazoles; D002250:Carbon Radioisotopes; D006634:Histamine H1 Antagonists; C043345:emedastine