Abstract
The ocular distribution, absorption and excretion of 14C-labeled or unlabeled tranilast after a single and repeated ophthalmic instillation were studied in guinea pigs and rabbits.
After a single administration in rabbits, the excretion ratio of radioactivity in urine, feces and expiration were similar both after an ophthalmic and oral administration ; and accumulated for approximately 30, 15 and 50% in urine, feces and expired air, respectively.
After a repeated ophthalmic instillation in rabbit eyes, the excretion ratio of radioactivity in urine, feces and expiration were nearly of the same pattern as that after a single ophthalmic instillation. After a single ophthalmic instilation in guinea pig and rabbit eyes, the radioactivity was high in the extraocular tissues, conjunctiva and cornea, than that in the intraocular tissues.
And the levels of tranilast in plasma were much lower than that in conjunctiva and in cornea.
The radioactivity of the ocular tissues during the repeated ophthalmic instillation in rabbit eyes was much higher in conjunctiva and in cornea than in other tissues, and continued to increase till the final dosing. The elimination ratio from these tissues after final dose of repeated ophthalmic instillation were comparative to the values after a single ophthalmic instillation. These results suggested that tranilast accumulated in the ocular tissues by consecutive instillation of 0.5% tranilast ophthalmic solution, but it did not remain in the ocular tissues after the cessation of instillation.
