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Improving the Therapeutic Index of Topically Applied Ocular Drugs
Thom J. Zimmerman, MD, PhD;
Karanjit S. Kooner, MD;
Artemios S. Kandarakis, MD;
Leigh P. Ziegler
Arch Ophthalmol. 1984;102(4):551-553.
Abstract
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• 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.
Author Affiliations
From the Department of Ophthalmology, Ochsner Clinic and Alton Ochsner Medical Foundation, and the Louisiana State University Eye Center, New Orleans.
Footnotes
Accepted for publication Dec 13, 1983.
Read in part before the annual meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Fla, May 3, 1983.
Reprint requests to Louisiana State University Eye Center, 136 S Roman St, New Orleans, LA 70112 (Dr Zimmerman).
This study was supported in part by US Public Health Service grants EY00115 and EY02376 from the National Eye Institute, National Institutes of Health, Bethesda, Md, and a departmental award (Ochsner) from Fight for Sight, Inc, New York.
Martin Hichens, PhD, and Irving Katz, MD, of Merck, Sharp & Dohme, West Point, Pa, performed the assay of all blood samples.
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