Pharmacokinetic and Pharmacodynamic Analysis of Systemic Effect of Topically Applied Timolol Maleate Ophthalmic Gelling Vehicle (Rysmon® TG)
Pharmacokinetic and Pharmacodynamic Analysis of Systemic Effect of Topically Applied Timolol Maleate Ophthalmic Gelling Vehicle (Rysmon® TG)
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DOI：
10.1080/02713680590923294
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发表时间：
2005-01-01
影响因子：
2
通讯作者：
Takayanagi, Risa
中科院分区：
文献类型：
--
作者：
Ohno, Yoshiyuki;Iga, Tatuji;Takayanagi, Risa
目的：评价马来酸噻吗洛尔眼用凝胶剂在人体内的全身吸收程度及全身不良反应。方法：以志愿者为研究对象，采用两阶段随机交叉设计。在一个阶段，志愿者滴入一滴0.5%的马来酸噻吗洛尔眼用凝胶剂；在另一个阶段，志愿者滴入一滴0.5%的马来酸噻吗洛尔眼用溶液。分别在接下来的120min和60min内观察两组的血药浓度和心率变化。结果：马来酸噻吗洛尔眼用凝胶剂的血药浓度时间曲线下面积(AUC)小于马来酸噻吗洛尔眼用液剂(p<；0.05)。眼用凝胶剂和滴眼液的心率无明显差异。用药动学和药效学模型可以成功地分析计算的β-肾上腺素能受体占有率与滴注后全身副作用之间的相关性，表明该模型对噻吗洛尔的全身副作用具有可预测性。结论：分析结果表明，马来酸噻吗洛尔眼用凝胶剂的全身吸收低于滴眼液，但全身作用的差异程度可忽略不计。
Purpose: The objective of this study was to evaluate the degree of systemic absorption and the systemic side effect after instillation of timolol maleate ophthalmic gelling vehicle in human. Methods: A volunteer study was employed, and a randomized crossover design with the two phases was used. In one phase, the volunteers instilled a single drop of the 0.5% timolol maleate ophthalmic gelling vehicle; in the other phase, the volunteers instilled a single drop of the 0.5% timolol maleate ophthalmic solution. The plasma concentration of timolol and the heart rates were studied during the following 120 min and 60 min, respectively. Results: The area under the blood concentration time curve (AUC) in timolol maleate ophthalmic gelling vehicle was lower than that in timolol maleate ophthalmic solution (p < 0.05). No differences were observed in heart rates between ophthalmic gelling vehicle and ophthalmic solution. The correlation between the calculated occupancy of beta-adrenergic receptors and the systemic side effects after instillation could be successfully analyzed with a pharmacokinetic and pharmacodynamic model, showing the predictability of the model for the systemic side effects of timolol. Conclusions: The result of our analysis clearly shows that timolol maleate ophthalmic gelling vehicle reduced the systemic absorption below that of ophthalmic solution, but the degree in difference of systemic effects was negligible.