Pharmacokinetics of falintolol II. Absorption, distribution and elimination from tissues and organs following ocular administration and intravenous injection of falintolol in albino rabbits.

The absorption, distribution and elimination of falintolol maleate was studied in various ocular and extraocular tissues and organs following ocular instillation, intravenous injection of a 0.5% 14C-falintolol ophthalmic solution and repeated ocular instillations of a 1% non-labeled falintolol ophthalmic solution into albino New Zealand rabbits. Falintolol was distributed in all studied tissues and organs after both routes of administration. After ocular instillation, levels of total radioactivity were distinctly higher in ocular tissues than after intravenous injection. Thus, the level was 475 times more important in cornea, 72 times in aqueous humor and 36 times in iris and ciliary body after ocular instillation. On the other hand, levels of total radioactivity in extraocular tissues and organs were 30-50% higher after intravenous injection compared to ocular instillation of the same dose. Peak levels of total radioactivity were generally achieved between 30 min and 1 h after ocular instillation, while 1.5 h after intravenous injection an increase in the declining part of the curve occurred. This increase, characteristic of an enterohepatic reabsorption, was also observed in blood and plasma 1 h after intravenous injection. Urinary elimination was the major means of excretion since 79.6% of total radioactivity was found in urine 6 h after intravenous injection and 74.5% 12 h after ocular instillation. But after ocular instillation, only 5% was excreted as unchanged falintolol. Whatever the route of administration, after single or repeated application, no drug accumulation was evident.