Intestinal permeability of ophthalmic beta-blockers for predicting ocular permeability.
The purpose of this study was to investigate the intestinal permeability of ophthalmic beta-blockers and evaluate the utility of intestinal membrane for predicting the ocular permeability. The penetrations of beta-blockers were measured across the isolated jejunum and colon of the albino rabbit using a two-chamber glass diffusion cell. beta-Blockers tested include atenolol, carteolol, tilisolol, timolol, and befunolol. Colonic membrane showed lower permeability of hydrophilic drugs than jejunal membrane. Scraping the entire cell monolayer of jejunum increased the drug permeability. There was a significant correlation between colonic permeability coefficients and lipophilicities of beta-blockers. The permeability coefficients through jejunum and scraped jejunum were not susceptible to drug lipophilicities. Jejunum, scraped jejunum, and colon showed permeability coefficients almost equal to those of sclera, conjunctiva, and cornea, respectively. There was a significant correlation between permeability coefficients through colon and cornea. These results indicate that the steady-state permeability of ophthalmic beta-blockers through ocular membranes may be predicted by measuring the permeability through certain intestinal membranes. However, the analyses of intestinal permeability using Fick's equation showed the functional difference of intestinal permeability from ocular permeability of ophthalmic beta-blockers.
Sasaki
H
H
School of Pharmaceutical Sciences, Nagasaki University, Japan.
Igarashi
Y
Y
Nishida
K
K
Nakamura
J
J
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000378:metabolism; D004058:Diffusion; D005123:Eye / Q000378:metabolism*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000502:physiology*; D007583:Jejunum / Q000378:metabolism; D008297:Male; D010539:Permeability; D011817:Rabbits
D000319:Adrenergic beta-Antagonists