Basis for Dosing Time-Dependent Changes in the Ocular and Systemic Absorption of Topically Applied Timolol
Autor: | Martina Barbara Sintzel, Hiroshi Yamahara, Samir K. Podder, Luc P. Balant, Myriam Martenet, Shigehiro Ohdo, Vincent H.L. Lee, Robert Gurny, Marianne Gex-Fabry |
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Rok vydání: | 1996 |
Předmět: |
Male
Time Factors genetic structures Administration Topical medicine.medical_treatment Biological Availability Timolol Pharmacology Absorption Corneal permeability Cornea Pharmacokinetics Anterior Eye Segment medicine Animals Anesthesia Pharmacology (medical) Dosing Administration Intranasal Chromatography High Pressure Liquid Analysis of Variance Ussing chamber Chemistry Systemic absorption Eye drop Adrenergic beta-Agonists eye diseases Circadian Rhythm Ophthalmology medicine.anatomical_structure Rabbits sense organs Conjunctiva medicine.drug |
Zdroj: | Journal of Ocular Pharmacology and Therapeutics. 12:103-113 |
ISSN: | 1557-7732 1080-7683 |
DOI: | 10.1089/jop.1996.12.103 |
Popis: | The objective of the present study was to determine the basis for dosing time-dependent changes in the ocular and systemic absorption of topically applied timolol in pigmented rabbits. The gamma scintigraphic technique was used to monitor the changes in precorneal solution retention following instillation. Changes in timolol concentration in the plasma over 120 min and in various anterior segment eye tissues at 30 min following the topical instillation of 25 microliters of 0.65% timolol maleate solutions at various dosing times were monitored using reversed phase HPLC. Corneal and conjunctival permeability at various dosing times was evaluated in the modified Ussing chamber. The results indicated that precorneal solution drainage was slowest at noon. Suppressing tear production by anesthesia led to an increase in ocular timolol absorption at 6 a.m. but not at other dosing times, in spite of the lowest corneal permeability then. There was no statistically significant dosing time influence on systemic timolol absorption following nasal or conjunctival dosing. In conclusion, possible diurnal changes in precorneal solution clearance may be the main factor underlying the diurnal changes in ocular as well as systemic timolol absorption in rabbits. In addition, diurnal changes in corneal permeability may also contribute to diurnal changes in ocular timolol absorption. |
Databáze: | OpenAIRE |
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