Pharmacokinetic study in the eye tissues after instillation of indomethacin into conjunctival cul-de-sac

A single dose of 70 μ1 0.125% 2-（14c）-indomethacin was dropped into conjunctival cul-de-sac of rabbit eye.The radio-activity in the tissues was tested by scintillation count and the counts per minute（cpm）was conversed into the concentration of the drug.The time-coured of indomethacin in lacrymal fluid,aqueous humor and eye tissues was studied and some important pharmacokinetec parameters were obtained.In the very early period after the drug was givien,the concentration of the drug in lacrymal fluid was highest in all of the samples of eye studied.The concentration in the cornea was the highest 15 minutes later and it in iris,ciliary,dody,aqueous humor,lens and vitreous was decreased successively.The timecourse of indomethacin in lacrymal fluid and cornea showed biexponential decrease.This process was also taken by aqueous humor in decreasing phase but with an absorptio phase.While in the iris and ciliary body the course showed rapid transfer from aqueous humor into these two tissues,this was followed by slow mono exponential decrease. The concentration of the drug in lens and vitreous was very low.It appears that the tissues of cormea,iris and ciliary body has a strong affinity to indomethacin,so that a higher concentration of the drug was kept in these tissues and eliminated in very slow rate,and the drug half-time in these tissues was relative longer than in lacrymal fluid and aqueous humor.On this theoretical basis,the interval between instilations should be longer when of the drug was used clinically. Since the concentration in lacrymal fluid was very close to that in cornea,it is possible to predict the concentration in cornea or intraocular tissue by measuring the concentration in lacrymal fluid.