文章基本信息

标题：Pharmacokinetic Prediction of the Ocular Absorption of an Instilled Drug with Ophthalmic Viscous Vehicle
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作者：Hitoshi SASAKI ; Kenzo YAMAMURA ; Takahiro MUKAI 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：2000
卷号：23
期号：11
页码：1352-1356
DOI：10.1248/bpb.23.1352
出版社：The Pharmaceutical Society of Japan
摘要：We previously developed an in vivo pharmacokinetic model that accounts for the corneal diffusion in albino rabbits and predicts the concentration of deta-blockers in the anterior segments. The purpose of this study is to pharmacokinetically predict the ocular absorption and characterize the systemic absorption of instilled drug with ophthalmic viscous vehicle to assist in its design and evaluation. Tilisolol and carboxymethylcellulose sodium salt (CMC) were used as the model ophthalmic drug and viscous polymer, respectively. After instillation of tilisolol with CMC vehicle in rabbits, the disposition of the drug in tear fluid, aqueous humor, and plasma were determined by HPLC. The ocular and systemic absorption were analyzed by a mathematical model including a diffusion process and a two-compartment model with first-order absorption, respectively. CMC vehicle increased the area under the concentration-time curve (AUC) of tilisolol in the tear fluid and aqueous humor and slightly reduced the AUC in plasma. The concentrations of tilisolol in the aqueous humor after instillation with CMC vehicle were accurately predicted from the tear concentrations by using the in vivo ocular pharmacokinetic model. CMC vehicle improved the ocular delivery of tilisolol.
关键词：eye;pharmacokinetics;diffusion equation;viscous vehicle;delivery system