Improving the ocular to systemic ratio of topical timolol by varying the dosing time.
Improving the ocular to systemic ratio of topical timolol by varying the dosing time.
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DOI：
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发表时间：
1991-09
影响因子：
4.4
通讯作者：
S. Ohdo;G. Grass;V. Lee
中科院分区：
文献类型：
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作者：
S. Ohdo;G. Grass;V. Lee
进行本研究的目的是确定是否可以通过改变滴注时间来最大程度地提高色素兔子局部应用的噻吗洛尔的眼部吸收与全身吸收的比率。上午 6 点、中午 12 点、下午 6 点或上午 12 点将 25 微升 0.65% 马来酸噻吗洛尔溶液滴入有色素的兔眼。使用反相高效液相色谱（HPLC）监测血浆和各种眼组织（结膜、巩膜、角膜上皮、角膜基质、房水、虹膜睫状体和晶状体）中噻吗洛尔浓度的时间进程。中午 12 点给药时，噻吗洛尔的眼浓度大约是上午 6 点、下午 6 点或上午 12 点时的两倍，而当中午 12 点给药时，血浆中噻吗洛尔的浓度最低。因此，通过在中午 12 点给药，可以最大限度地提高局部应用噻吗洛尔的治疗指数。此外，在规划局部眼科药物的给药方案时，必须考虑给药时间对眼部和全身药物吸收程度的可能影响。
This study was performed to determine whether the ratio of ocular to systemic absorption of topically applied timolol in the pigmented rabbit can be maximized by varying the time of drop instillation. Twenty-five microliters of 0.65% timolol maleate solutions were instilled into the pigmented rabbit eye at 6 AM, 12 PM, 6 PM, or 12 AM. The time course of timolol concentration in plasma and various eye tissues (conjunctiva, sclera, corneal epithelium, corneal stroma, aqueous humor, iris-ciliary body, and lens) was monitored with the use of reversed phase high-performance liquid chromatography (HPLC). Ocular timolol concentrations were approximately twice as high when the drug was administered at 12 PM than at 6 AM, 6 PM, or 12 AM, whereas timolol concentration in plasma was lowest when the drug was administered at 12 PM. It may, therefore, be possible to maximize the therapeutic index of topically applied timolol by administering the drug at 12 PM. Moreover, the possible influence of dosing time on the extent of ocular and systemic drug absorption must be considered when planning dosing schedules for topically applied ophthalmic drugs.