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Ocular Intracameral Pharmacokinetics for a Cocktail of Timolol, Betaxolol, and Atenolol in Rabbits.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-01-09 , DOI: 10.1021/acs.molpharmaceut.9b01024 Anam Fayyaz 1, 2 , Veli-Pekka Ranta 2 , Elisa Toropainen 2 , Kati-Sisko Vellonen 2 , Giuseppe D'Amico Ricci 3, 4 , Mika Reinisalo 2, 5 , Emma M Heikkinen 2 , Iain Gardner 1 , Arto Urtti 2 , Masoud Jamei 1 , Eva M Del Amo 6
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-01-09 , DOI: 10.1021/acs.molpharmaceut.9b01024 Anam Fayyaz 1, 2 , Veli-Pekka Ranta 2 , Elisa Toropainen 2 , Kati-Sisko Vellonen 2 , Giuseppe D'Amico Ricci 3, 4 , Mika Reinisalo 2, 5 , Emma M Heikkinen 2 , Iain Gardner 1 , Arto Urtti 2 , Masoud Jamei 1 , Eva M Del Amo 6
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The mechanisms of drug clearance from the aqueous humor are poorly defined. In this study, a cocktail approach was used to simultaneously determine the pharmacokinetics of three β-blocker agents after intracameral (ic) injection into the rabbit eyes. Aqueous humor samples were collected and analyzed using LC-MS/MS to determine drug concentrations. Pharmacokinetic parameters were obtained using a compartmental fitting approach, and the estimated clearance, volume of distribution, and half-life values were the following: atenolol (6.44 μL/min, 687 μL, and 73.87 min), timolol (19.30 μL/min, 937 μL, and 33.64 min), and betaxolol (32.20 μL/min, 1421 μL, and 30.58 min). Increased compound lipophilicity (atenolol < timolol < betaxolol) resulted in higher clearance and volume of distributions in the aqueous humor. Clearance of timolol and betaxolol is about 10 times higher than the aqueous humor outflow, demonstrating the importance of other elimination routes (e.g., uptake to iris and ciliary body and subsequent elimination via blood flow).
中文翻译：
眼内肌药代动力学在兔子中的替莫洛尔，倍他洛尔和阿替洛尔的鸡尾酒。
从房水清除药物的机制定义不清。在这项研究中，采用鸡尾酒法同时测定了前房内（ic）注入兔眼后三种β受体阻滞剂的药代动力学。收集房水样品并使用LC-MS / MS分析以确定药物浓度。使用隔室拟合方法获得药代动力学参数，估计的清除率，分布体积和半衰期值如下：阿替洛尔（6.44μL/ min，687μL和73.87 min），噻吗洛尔（19.30μL/ min， 937μL和33.64分钟）和倍他洛尔（32.20μL/ min，1421μL和30.58分钟）。化合物亲脂性的提高（阿替洛尔<噻吗洛尔<紫杉醇）导致房水中较高的清除率和分布体积。
更新日期：2020-01-09
中文翻译：
眼内肌药代动力学在兔子中的替莫洛尔，倍他洛尔和阿替洛尔的鸡尾酒。
从房水清除药物的机制定义不清。在这项研究中，采用鸡尾酒法同时测定了前房内（ic）注入兔眼后三种β受体阻滞剂的药代动力学。收集房水样品并使用LC-MS / MS分析以确定药物浓度。使用隔室拟合方法获得药代动力学参数，估计的清除率，分布体积和半衰期值如下：阿替洛尔（6.44μL/ min，687μL和73.87 min），噻吗洛尔（19.30μL/ min， 937μL和33.64分钟）和倍他洛尔（32.20μL/ min，1421μL和30.58分钟）。化合物亲脂性的提高（阿替洛尔<噻吗洛尔<紫杉醇）导致房水中较高的清除率和分布体积。
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