In situ ocular absorption of tilisolol through ocular membranes in albino rabbits.
The purpose of this study is to characterize the in situ absorption properties of ocular membranes using a cylindrical cell. Drug disappearance in the cell was determined as in situ absorption after an application of drug solution into the cell on the comea, sclera (bulbar conjunctiva and sclera layer), or palpebral conjunctiva. Tilisolol was used as a model of an ophthalmic beta-blocker. Tilisolol disappeared from the conjunctival and scleral surfaces although hardly any disappearance of tilisolol from the corneal surface was observed. Depletion of drug from the precorneal space was much faster in situ than extrapolated from permeability measurements (in vitro) of the separate tissues. This may arise from an influence of blood flow. The in situ apparent permeability coefficient of tilisolol through the conjunctiva was almost constant at various concentrations of drug (5-100 mM), suggesting a passive diffusion of tilisolol that was affected by medium pH. A high concentration of tilisolol in the aqueous humor was observed in the corneal application although the scleral and conjunctival applications showed a slight concentration of tilisolol. The corneal route was a dominant route of access to the aqueous humor. Access to the vitreous body for tilisolol was 4 times more effective through the sclera than through the cornea. On the other hand, the corneal application showed an extremely low concentration of tilisolol in plasma compared to the scleral and conjunctival applications. Thus, the in situ method using a cylindrical cell is a useful method for investigation of the ocular absorption of ophthalmic drugs.
Sasaki
H
H
Department of Hospital Pharmacy, Nagasaki University School of Medicine, Japan.
Ichikawa
M
M
Kawakami
S
S
Yamamura
K
K
Nishida
K
K
Nakamura
J
J
D000042:Absorption; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D005123:Eye / Q000378:metabolism*; D007546:Isoquinolines / Q000493:pharmacokinetics*; D008297:Male; D011817:Rabbits; D014822:Vitreous Body / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D007546:Isoquinolines; C036593:tilisolol