title: Penetration and binding of aldose-reductase inhibitors in the lens.
abstract: Diffusion, partitioning, and binding of two aldose-reductase inhibitors (ARI) in the rat lens were investigated under in vitro conditions. A lipophilic ARI (CT-112) and a hydrophilic ARI (AD-5467) were used as model drugs. Under lens-uptake conditions, the drug concentration in the lens increased rapidly during the initial 10 hr and reached steady state (equilibrium) after 24 hr. Despite the equilibrium concentration of CT-112 in the lens which is approximately three times of that of AD-5467, the inhibition rate of CT-112 against the accumulation of sugar alcohols was appreciably lower than that for AD-5467. The equilibrium concentration in the lens after the penetration/binding experiment also suggested that AD-5467 may interact with the target sites of enzymes more than that for CT-112. The time course of the lens concentration during the uptake and desorption experiments was well described by a diffusion/binding model assuming a Langmuir binding. The diffusion coefficient, the partition coefficient, and binding parameters in the rat lens were determined for the two ARIs.
authors.affiliation: Itami Research Laboratories, Senju Pharmaceutical Co., Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ohtori
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: K J
authors.initials: KJ
authors.lastname: Tojo
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D004058:Diffusion; D007908:Lens, Crystalline / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009924:Organ Culture Techniques; D010078:Oxazines / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013012:Sorbitol / Q000378:metabolism; D013844:Thiazoles / Q000493:pharmacokinetics*; D045162:Thiazolidinediones; D014993:Xylitol / Q000378:metabolism
chemical_list: D010078:Oxazines; D013844:Thiazoles; D045162:Thiazolidinediones; C065301:AD 5467; D013012:Sorbitol; C051003:risarestat; D000449:Aldehyde Reductase; D014993:Xylitol