Penetration of timolol into the rabbit eye. Measurements after ocular instillation and intravenous injection
C. J. Schmitt, V. J. Lotti and J. C. LeDouarec
The distribution of radioactivity in 15 ocular and extraocular tissues or
fluids of the rabbit after ocular instillation and intravenous injection of
100 microL of 14C-labeled timolol solution (1.5%) was studied by liquid
scintillation counting (LSC). The drug was distributed rapidly among the
tissues examined after both routes of administration. Levels of
radioactivity were considerably greater in ocular tissues after
instillation as compared with intravenous injection, whereas in extraocular
tissues the levels were similar after both routes of administration. Using
the same experimental protocol, aqueous humor and serum levels of unchanged
timolol were measured by gas liquid chromatography. Comparisons with LSC
studies indicated that, following ocular instillation, only unchanged
timolol was present in aqueous humor, whereas both timolol and metabolites
were present in serum. After intravenous administration, timolol was
rapidly metabolized and metabolites appeared in the serum and aqueous
humor.
