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Ocular Pharmacokinetic/Pharmacodynamic Modeling for Timolol in Rabbits Using a Telemetry System


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タイトル: Ocular Pharmacokinetic/Pharmacodynamic Modeling for Timolol in Rabbits Using a Telemetry System
著者: Sakanaka, Koji / Kawazu, Kouichi / Tomonari, Masahide / Kitahara, Takashi / Nakashima, Mikiro / Nishida, Koyo / Nakamura, Junzo / Sasaki, Hitoshi / Higuchi, Shun
発行日: 2008年 5月 1日
出版者: The Pharmaceutical Society of Japan
引用: Biological & Pharmaceutical Bulletin, 31(5), pp.970-975; 2008
抄録: 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.
キーワード: pharmacokinetic / pharmacodynamic / eye / timolol / telemetry system
URI: http://hdl.handle.net/10069/17913
ISSN: 09186158
DOI: 10.1248/bpb.31.970
権利: (c) 2008 The Pharmaceutical Society of Japan
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:130 学術雑誌論文

引用URI : http://hdl.handle.net/10069/17913

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