Absorption of ocular timolol: drug concentrations and beta-receptor binding activity in the aqueous humour of the treated and contralateral eye.
We studied the ocular and systemic absorption of 40 microliters of topical 0.5% timolol in 57 patients using radioligand binding techniques. The mean concentration of timolol in aqueous humour of the treated eye was 1.9 +/- 0.8 micrograms/ml 74 minutes after instillation of the drug. About 18 h after drug instillation the aqueous humour concentration of timolol was 105.5 +/- 60.9 ng/ml. Timolol was found in 15 (42%) contralateral eyes. Concentration of timolol in the contralateral eye increased from 0.04 +/- 0.08 ng/ml at 50 min to 0.3 +/- 0.2 ng/ml at 134 min and was 0.2 +/- 0.4 ng/ml at 18 h after instillation. Timolol concentrations in the aqueous humour of the treated eye appeared to be high enough to occupy beta 1- and beta 2-receptors completely (100%) at 74 min and at 18 h after drug instillation. Timolol concentrations in the contralateral eye were high enough to occupy up to 33.0 +/- 24.7% of the beta 2-receptors and up to 51.7 +/- 35.1% of beta 2-receptors. High drug concentrations and complete beta-receptor occupancy in the aqueous humour of the treated eye after topical timolol are in agreement with the long-lasting ocular hypotensive effects. The low drug concentrations and partial receptor occupancy in the contralateral eye may also be of some clinical significance.
Saari
K M
KM
Department of Ophthalmology, University of Turku, Finland.
Ali-Melkkilä
T
T
Vuori
M L
ML
Kaila
T
T
Iisalo
E
E
D000042:Absorption; D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000368:Aged; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D002387:Cataract Extraction; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007910:Lenses, Intraocular; D009883:Ophthalmic Solutions; D011412:Propanolamines / Q000378:metabolism; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013999:Timolol / Q000493:pharmacokinetics*
D000319:Adrenergic beta-Antagonists; D009883:Ophthalmic Solutions; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D013999:Timolol; C033394:CGP 12177