September 1991
Volume 32, Issue 10
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Articles  |   September 1991
Improving the ocular to systemic ratio of topical timolol by varying the dosing time.
Author Affiliations
  • S Ohdo
    Department of Pharmacology, Ehime University School of Medicine, Japan.
  • G M Grass
    Department of Pharmacology, Ehime University School of Medicine, Japan.
  • V H Lee
    Department of Pharmacology, Ehime University School of Medicine, Japan.
Investigative Ophthalmology & Visual Science September 1991, Vol.32, 2790-2798. doi:
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      S Ohdo, G M Grass, V H Lee; Improving the ocular to systemic ratio of topical timolol by varying the dosing time.. Invest. Ophthalmol. Vis. Sci. 1991;32(10):2790-2798.

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Abstract

This study was performed to determine whether the ratio of ocular to systemic absorption of topically applied timolol in the pigmented rabbit can be maximized by varying the time of drop instillation. Twenty-five microliters of 0.65% timolol maleate solutions were instilled into the pigmented rabbit eye at 6 AM, 12 PM, 6 PM, or 12 AM. The time course of timolol concentration in plasma and various eye tissues (conjunctiva, sclera, corneal epithelium, corneal stroma, aqueous humor, iris-ciliary body, and lens) was monitored with the use of reversed phase high-performance liquid chromatography (HPLC). Ocular timolol concentrations were approximately twice as high when the drug was administered at 12 PM than at 6 AM, 6 PM, or 12 AM, whereas timolol concentration in plasma was lowest when the drug was administered at 12 PM. It may, therefore, be possible to maximize the therapeutic index of topically applied timolol by administering the drug at 12 PM. Moreover, the possible influence of dosing time on the extent of ocular and systemic drug absorption must be considered when planning dosing schedules for topically applied ophthalmic drugs.

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