文章基本信息

标题：Ocular Pharmacokinetic/Pharmacodynamic Modeling for Timolol in Rabbits Using a Telemetry System
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作者：Koji Sakanaka ; Kouichi Kawazu ; Masahide Tomonari 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2008
卷号：31
期号：5
页码：970-975
DOI：10.1248/bpb.31.970
出版社：The Pharmaceutical Society of Japan
摘要：We have established an ocular pharmacokinetic/pharmacodynamic (PK/PD) model for a β-adrenergic antagonist, timolol, after instillation into rabbits. Timolol concentrations were determined by HPLC in the tear fluid, aqueous humor, cornea, and iris-ciliary body after instillation or ocular injection into the anterior chamber of the eye in rabbits. In addition, intraocular pressure (IOP) measurement was performed after instillation of timolol by a telemetry system, which was able to obtain detailed IOP data automatically. The PK/PD parameters were estimated by fitting the concentration–time profiles and the ocular hypotensive effect–time profiles using MULTI (RUNGE) program. The PK model consisted of six compartments and the PD model included aqueous humor dynamics based on an action mechanism of timolol, which causes lowering of IOP by suppressing aqueous humor production. The PK/PD model described well the concentration–time profiles and the ocular hypotensive effect–time profiles after instillation of timolol. This study is the first trial to develop an ocular PK/PD model for timolol after instillation. This model can predict both the drug concentrations in various ocular tissues and the ocular hypotensive effect after instillation of timolol.
关键词：pharmacokinetic;pharmacodynamic;eye;timolol;telemetry system