Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Vuori, M.L. et al.

Plasma kinetics and antagonist activity of topical ocular timolol in elderly patients.

BACKGROUND: Systemic adverse effects of ocular timolol therapy are due to absorption of the drug from the eye into the systemic circulation. Elderly patients are frequently more susceptible to side effects than younger patients. This study was conducted to evaluate the plasma kinetics and antagonist activity of ocular timolol in elderly patients. METHODS: Plasma kinetics and antagonist activity of timolol were studied in 12 patients scheduled for extracapsular cataract extraction and intraocular lens implantation. The patients received 40 microliters of 0.25% timolol into the lower cul-de-sacs of each eye. Blood samples were collected over a period of 12 h and plasma concentrations of timolol were analyzed using a radioreceptor assay. The corresponding ex vivo beta 1- and beta 2-receptor occupancies were calculated using radioligand binding techniques. RESULTS: Timolol was absorbed rapidly into the systemic circulation and occupied on average up to 68% of beta 1-receptors and up to 87% of beta 2-receptors. The beta 1- and beta 2-receptor occupancy decreased slowly and was on average 38% and 64%, respectively, 12 h after the single dose. The calculated mean area under concentration-time curve of timolol in plasma was 10.28 ng/ml per hour and the mean half-life was 4.8 h. Both values were about twice as high as those found in healthy young volunteers following an intravenous 0.25-mg dose of timolol. CONCLUSIONS: In elderly patients the beta-receptor antagonist effect of ocular timolol after a single dose is strong and long-lasting. This finding may explain the frequent reported systemic side effects of ophthalmic timolol.[1]

References

Plasma kinetics and antagonist activity of topical ocular timolol in elderly patients. Vuori, M.L., Kaila, T. Graefes Arch. Clin. Exp. Ophthalmol. (1995) [Pubmed]

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