Absorption characteristics of model compounds from the small intestinal serosal surface and a comparison with other organ surfaces.
We examined the absorption of phenolsulfonphthalein (PSP) and fluorescein isothiocyanate dextrans (FD-4, MW 4400; FD-10, MW 9500; FD-40, MW 40 500) as model compounds through the small intestinal serosal surface. After application to the rat small intestinal serosal surface using a cylindrical diffusion cell, each compound was absorbed at different rates. The absorption ratios in 6 h after PSP, FD-4, FD-10 and FD-40 application were calculated to be 89.2, 34.6, 14.9 and 2.1% of dose, respectively. Elimination profiles of PSP, FD-4 and FD-10 from the small intestinal serosal surface obeyed first-order kinetics. Moreover, we calculated the apparent permeability coefficient P(app) for comparison to other organ surfaces. The kidney had the highest absorption efficiency, as shown by having more than 1.5 times significantly higher P(app) values of PSP, FD-4 and FD-10. Similar to the other organ surfaces, a correlation was observed between the P(app) of the small intestine and the molecular weight of these hydrophilic compounds. In addition, the small intestine is likely to contribute largely to hydrophilic compound absorption from the peritoneal cavity, judging from absorption clearance, CL(a), calculated using the peritoneal organ surface area.
Nishida
Koyo
K
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. koyo-n@net.nagasaki-u.ac.jp
Kuma
Akiko
A
Fumoto
Shintaro
S
Nakashima
Mikiro
M
Sasaki
Hitoshi
H
Nakamura
Junzo
J
D000818:Animals; D001646:Bile / Q000378:metabolism; D003911:Dextrans / Q000493:pharmacokinetics* / Q000652:urine; D004058:Diffusion; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism / Q000502:physiology*; D007668:Kidney / Q000502:physiology; D008297:Male; D008970:Molecular Weight; D010637:Phenolsulfonphthalein / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D010637:Phenolsulfonphthalein