Lipophilicity influence on conjunctival drug penetration in the pigmented rabbit: a comparison with corneal penetration.
The influence of lipophilicity on the conjunctival penetration of beta blockers in the pigmented rabbit was investigated and compared with that on corneal penetration. The beta blockers were hydrophilic sotalol, atenolol, nadolol, pindolol, and acebutolol; lipophilic metoprolol, timolol, oxprenolol, levobunolol, labetalol, and alprenolol; and the very lipophilic propranolol and betaxolol. Drug penetration was evaluated by using the isolated pigmented rabbit conjunctiva and cornea in the modified Ussing chamber and was monitored by reversed phase HPLC. The conjunctiva was more permeable to all the beta blockers than was the cornea. A sigmoidal relationship, rather than the familiar parabolic relationship, best described the influence of lipophilicity on both conjunctival and corneal drug penetration. The ratio of corneal to conjunctival permeability coefficients was most sensitive to changes in log PC within the region of 1.5 and 2.5. Outside of this region, the ratio was relatively independent of changes in lipophilicity. For several beta blockers, their intrinsic sympathomimetic activity may play a minor role in influencing their conjunctival and corneal penetration.
University of Southern California, School of Pharmacy, Department of Pharmaceutical Sciences, Los Angeles 90033.
W
W
Wang
H
H
Sasaki
D S
DS
Chien
V H
VH
Lee
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003228:Conjunctiva / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism*; D008055:Lipids / Q000502:physiology*; D008297:Male; D010539:Permeability; D011817:Rabbits; D012995:Solubility; D014018:Tissue Distribution
D000319:Adrenergic beta-Antagonists; D008055:Lipids