Uptake and distribution of chlorpromazine in animal eyes

[ 35 S]Chlorpromazine was orally administered daily to dogs for periods up to 4 weeks. Considerable amounts of labeled material were present in the uveal tissue after the first week, and the concentration reached a maximum at the end of the third week. No detectable labeled material was found either in the cornea or lens after 4 weeks, and only trace amounts were detected in the anterior aqueous humor. The ability of the uvea to take up the drug after intravenous administration was depressed by 55% after oral pretreatment with nonradioactive drug for 3 weeks. Similar studies with pigmented and albino rabbits showed that the labeled material accumulated only in the pigmented uvea. Maximum levels of accumulation were attained after 3 weeks, and then the concentration fell 80% to a steady-state level, which was maintained for the duration of the experiments. No detectable labeled material was found in the cornea, lens, or aqueous humor of the anterior chamber. Discontinuation of the drug after the third week resulted in a slow disappearance of labeled material from the uvea. When nonlabeled drug was administered after the third week, rapid exchange of the labeled material in the uvea occurred. The labeled material in all experiments was separated into two pools, one containing the drug that was extracted at pH 8·4 with ethyl acetate and the other containing the drug that was not extractable with ethyl acetate.