Urtti A, Sendo T, Pipkin J D, Rork G, Repta A J
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence.
J Ocul Pharmacol. 1988 Winter;4(4):335-43. doi: 10.1089/jop.1988.4.335.
Ocular absorption of timolol in rabbits was studied after topical ocular administration of 3H-timolol in an eyedrop or in silicone cylindrical devices that released timolol at 7.2 micrograms/h. The devices were applied in either the inferior or superior conjunctival sac. Timolol concentrations were nearly equal in the inferior and superior portions of ocular tissues when the drug was administered in an eyedrop. Administration in the devices resulted in unequal timolol distribution in the cornea, conjunctiva, sclera, and iris-ciliary body. Timolol concentrations were higher in the part of each tissue that was closer to the site of the device application. Unequal concentrations of timolol in the superior and inferior part of the eye and very low timolol concentrations in the aqueous humor indicated that timolol was absorbed mainly via a noncorneal route from the device placed in the inferior conjunctival sac. Induced blinking at one minute intervals did not change ocular absorption of timolol. Compared with inferior conjunctival sac applications, placement of the devices in the superior conjunctival sac resulted in increased corneal and total ocular absorption of timolol as indicated by higher timolol concentrations in the aqueous humor and by a smaller difference between concentrations in the superior and inferior portions of the examined tissues. The application site dependent ocular absorption indicated that controlled release of timolol in the tear fluid did not result in a uniform timolol distribution in the preocular tear fluid of rabbit eyes.
在兔眼局部滴注³H-噻吗洛尔滴眼液或置于结膜囊的硅胶圆柱型装置（以7.2微克/小时的速率释放噻吗洛尔）后，研究了噻吗洛尔的眼部吸收情况。装置分别置于下结膜囊或上结膜囊。当以滴眼液形式给药时，眼组织的下部和上部的噻吗洛尔浓度几乎相等。通过装置给药导致噻吗洛尔在角膜、结膜、巩膜和虹膜睫状体中的分布不均。在每个组织中，靠近装置应用部位的部分噻吗洛尔浓度更高。眼的上部和下部噻吗洛尔浓度不均，且房水中噻吗洛尔浓度极低，这表明噻吗洛尔主要通过非角膜途径从置于下结膜囊的装置吸收。每隔一分钟诱导眨眼并未改变噻吗洛尔的眼部吸收。与下结膜囊给药相比，将装置置于上结膜囊导致噻吗洛尔在角膜和全眼的吸收增加，这表现为房水中噻吗洛尔浓度更高，且在所检查组织的上部和下部浓度之间的差异更小。噻吗洛尔眼部吸收的部位依赖性表明，泪液中噻吗洛尔的控释并未导致兔眼前房泪液中噻吗洛尔分布均匀。
