Lack of metabolism of timolol by ocular tissues.

The ocular metabolism of timolol has been studied in the iris/ciliary body, vitreous humor, neuro-retina and cornea from an albino rabbit, pigmented rabbit and cynomolgus monkey by incubating tissues isolated from these animals with radiolabeled drug for 20 hours at 37 degrees C in Hanks' balanced salts solution. After removal of the tissues by centrifugation and subsequent deproteinization, supernatants were mixed with unlabeled timolol and analyzed by isocratic reverse phase high performance liquid chromatography with liquid scintillation counting and ultraviolet detection. Although this analytical system readily demonstrated the production of timolol metabolites by rat liver, the production of timolol metabolites by ocular tissues could not be demonstrated. With most samples high recoveries of unmetabolized timolol were obtained. The lowest level of recovery of unmetabolized drug as compared to a control (drug added after the tissue had been incubated) was obtained for the iris/ciliary body from the pigmented rabbit suggesting that pigment had bound the drug. Our results suggest that deleterious side effects sometimes seen with the drug or its lack of efficacy with rabbits is not due to ocular metabolism by these tissues.