Pharmacokinetics for topically applied caffeine in the rat

•Topical caffeine penetrates to the lens and blood in rats.•Caffeine quickly accumulates in the lens with a slow washout, whereas caffeine slowly accumulates in the blood.•The accumulation of caffeine in lens and blood is directly proportional to its topically applied dose.•Rat caffeine blood levels achieved are far below the equivalent threshold dose of FDA recommended daily dose for humans.•No toxic effects are observed on eyelids, conjunctiva, cornea and lens.

Topically applied caffeine was recently identified as a promising candidate molecule for cataract prevention. Little is known about the pharmacokinetics for topically applied caffeine. Potential toxicity of 72 mM caffeine on the ocular surface and the lens was qualitatively monitored and no toxic effects were observed. The concentration of caffeine was measured in the lens and the blood after topical application of 72 mM caffeine to groups of 10 animals sacrificed at 30, 60, 90 and 120 min after topical application. The lens concentration decreased throughout the observation period while the blood concentration increased up to 120 min. Further, the concentration of caffeine in the lens and blood was measured 30 min after topical application of caffeine, the concentration of caffeine being 0.72, 3.34, 15.51 and 72 mM depending on group belonging, in groups of 10 animals. The caffeine concentration in lens and blood, respectively, increased proportionally to the caffeine concentration topically applied. The rat blood concentrations achieved were far below the equivalent threshold dose of FDA recommended daily dose for humans. This information is important for further development of caffeine eye drops for cataract prevention.