Permeability characteristics of primary cultured rabbit conjunctival epithelial cells to low molecular weight drugs.
OBJECTIVE
To evaluate the permeability characteristics of primary cultured rabbit conjunctival epithelial cell (RCEC) layers to low molecular weight drugs of varying lipophilicity.


METHODS
3H-mannitol; hydrophilic sotalol and atenolol; moderately lipophilic metoprolol, timolol, propranolol; and highly lipophilic betaxolol were used as model compounds.


RESULTS
The conjunctival apparent permeability coefficient (Papp) of mannitol (1 x 10(-7) cm/s) was 2.4 times lower than that of the most hydrophilic beta-blocker, sotalol (Papp = 2.4 x 10(-7) cm/s). Differences in the degree of tightness of the epithelial cell layers brought about a 30-fold difference in the transport of atenolol in favor of the leaky cell layers, while not affecting the transport of the lipophilic drug, propranolol. Within the log partition coefficient (PC) range of -0.62 (sotalol) and 3.44 (betaxolol), there was a hundred-fold difference in the Papp. A sigmoidal curve was used to depict the influence of lipophilicity on solute permeation across conjunctival epithelial cell layers. An effective half-maximal Papp was observed at a log PC value of 1.2.


CONCLUSIONS
These findings on the lipophilicity effect on drug transport are generally similar to those reported for the isolated rabbit conjunctiva, suggesting the utility of cultured rabbit conjunctival epithelial cell layers as an in vitro model for evaluating drug transport.
Saha
P
P
Department of Pharmaceutical Sciences and Ophthalmology, University of Southern California, Los Angeles, USA.
Uchiyama
T
T
Kim
K J
KJ
Lee
V H
VH
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003228:Conjunctiva / Q000166:cytology / Q000378:metabolism*; D004234:Diuretics, Osmotic / Q000493:pharmacokinetics; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D008353:Mannitol / Q000493:pharmacokinetics; D008970:Molecular Weight; D011817:Rabbits; D019108:Tight Junctions / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D004234:Diuretics, Osmotic; D008353:Mannitol