Improving the therapeutic index of topically applied ocular drugs
T. J. Zimmerman, K. S. Kooner, A. S. Kandarakis and L. P. Ziegler
Nasolacrimal occlusion (NLO) and eyelid closure are simple techniques that
not only increase the ocular bioavailability of topically applied ocular
drugs but also reduce the probability of adverse systemic effects. Each
serves to improve the therapeutic index. Subsequent to the application of
0.5% timolol maleate, the effects of NLO and eyelid closure were compared
with the effects of no procedures. In this experiment, systemic drug
absorption in normal volunteers was reduced more than 60%. Measurements
were made by radioimmunoassay of timolol in blood plasma. In addition, the
diminution of fluorescein in the anterior chamber was observed for three
hours following direct application to the lower cul-de-sac. Results
indicate a lower fluorescein concentration and a shorter duration of
fluorescence in the absence of either experimental technique. Both NLO and
eyelid closure seem to be safe, simple, and effective procedures that could
minimize dosage requirements, as well as side effects.
