Corneal and conjunctival/scleral penetration of p-aminoclonidine, AGN 190342, and clonidine in rabbit eyes.

The ocular penetration pathways of three alpha 2-adrenergic agents (p-aminoclonidine, AGN 190342, and clonidine) were investigated in rabbits both in vitro and in vivo. The corneal permeabilities of the compounds correlated positively with their octanol/water distribution coefficients. The ocular drug absorption via corneal and conjunctival/scleral penetration routes was evaluated separately after drug perfusion in vivo. In most cases, the corneal route was the major pathway for the intraocular drug absorption. However, the conjunctival/scleral penetration pathway was the predominant pathway for the delivery of p-aminoclonidine, the least lipophilic compound among the three drugs, to the ciliary body. The drug concentration in the iris was contributed mainly by the corneal route and correlated well with drug lipophilicity.

[1]  R. Brubaker,et al.  Aqueous flow is reduced by the alpha-adrenergic agonist, apraclonidine hydrochloride (ALO 2145). , 1988, Ophthalmology.

[2]  A. Robin,et al.  The safety and efficacy of topical 1% ALO 2145 (p-aminoclonidine hydrochloride) in normal volunteers. , 1987, Archives of ophthalmology.

[3]  T. F. Patton,et al.  Disposition of timolol and inulin in the rabbit eye following corneal versus non-corneal absorption , 1987 .

[4]  T. F. Patton,et al.  Selective intraocular delivery of liposome encapsulated inulin via the non-comeal absorption route , 1986 .

[5]  J. Burke,et al.  Ocular effects of a relatively selective α2 agonist (UK-14, 304-18) in cats, rabbits and monkeys , 1986 .

[6]  T. F. Patton,et al.  Importance of the noncorneal absorption route in topical ophthalmic drug delivery. , 1985, Investigative ophthalmology & visual science.

[7]  R. Brubaker,et al.  Effect of clonidine on aqueous humor flow in normal human eyes. , 1984, Experimental eye research.

[8]  G. Chiou.  Effects of α1 and α2 activation of adrenergic receptors on aqueous humor dynamics , 1983 .

[9]  M. Kass,et al.  The effect of topical clonidine on intraocular pressure. , 1981, Archives of ophthalmology.

[10]  H. Lal,et al.  Clonidine: New research in psychotropic drug pharmacology , 1981, Medicinal research reviews.

[11]  T. Miyata,et al.  Soluble gentamicin ophthalmic inserts as a drug delivery system. , 1978, Archives of ophthalmology.

[12]  M. Doane,et al.  Penetration routes of topically applied eye medications. , 1978, American journal of ophthalmology.

[13]  M. Rawlins,et al.  Central nervous system depressant actions of clonidine and UK-14,304: partial dissociation of EEG and behavioural effects. , 1978, British journal of clinical pharmacology.

[14]  R. Harrison,et al.  Clonidine: Effects of a Topically Administered Solution on Intraocular Pressure and Blood Pressure in Open-Angle Glaucoma , 1977 .

[15]  D. S. Hull,et al.  Permeability of the isolated rabbit cornea to corticosteroids. , 1974, Investigative ophthalmology.

[16]  S. Hoobler,et al.  Comparison of clonidine and methyldopa on blood pressure and side effects in hypertensive patients. , 1972, American heart journal.

[17]  V. H. Lee,et al.  Topical ocular drug delivery: recent developments and future challenges. , 1986, Journal of ocular pharmacology.

[18]  I. Leopold,et al.  Alpha-adrenergic receptors in rabbit eyes. , 1985, Journal of ocular pharmacology.

[19]  M. Sears.  Autonomic Nervous System: Adrenergic Agonists , 1984 .

[20]  L. Bito,et al.  The penetration of exogenous prostaglandin and arachidonic acid into, and their distribution within, the mammalian eye. , 1981, Current eye research.