The ocular penetration of topical forskolin and its effects on intraocular pressure, aqueous flow rate and cyclic AMP level in the rabbit eye.
The ocular penetration of 14C-forskolin in suspension was studied using albino rabbits. The effects of topical forskolin suspension on cyclic AMP (cAMP) synthesis, aqueous flow and intraocular pressure (IOP) were also studied. It was shown that only 0.03% of the instilled forskolin penetrated the ocular tissue. The calculated kep value for forskolin was 0.2 X 10(-4) cm/hr. The peak concentrations were calculated to be 4 X 10(-7) mole/liter, 4.6 X 10(-7) and 2.7 X 10(-7) mole/1,000 g tissue in aqueous, iris and ciliary body, respectively, after instillation of 1% forskolin suspension. Topical 1% forskolin suspension caused cAMP increase in the aqueous humor 30 minutes after instillation, but cAMP returned to baseline level 60 minutes after instillation. The cAMP level in the ciliary body was not increased by forskolin. Aqueous flow did not change, and the IOP was slightly decreased 45 and 60 minutes after instillation of forskolin suspension. The in vivo least-effective concentration of forskolin in the ciliary epithelium was considered to be about 2.7 X 10(-7) mole/1,000 g tissue. The weak IOP lowering effect of topical forskolin suspension was considered to be due to its poor ocular penetration. However, slight modification of molecular structure might increase ocular penetration. Present results suggest only a slight increase in penetrative potential would be needed to make forskolin effective in antiglaucoma therapy.
Matsumoto
S
S
Department of Ophthalmology, University of Tokyo School of Medicine, Japan.
Yamashita
T
T
Araie
M
M
Kametani
S
S
Hosokawa
T
T
Takase
M
M
D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D002924:Ciliary Body / Q000187:drug effects; D005576:Colforsin / Q000493:pharmacokinetics* / Q000494:pharmacology; D003315:Cornea / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D007429:Intraocular Pressure / Q000187:drug effects*; D007498:Iris / Q000187:drug effects; D011817:Rabbits; D014018:Tissue Distribution
D005576:Colforsin; D000242:Cyclic AMP