Urtti A, Rouhiainen H, Kaila T, Saano V
Department of Pharmaceutical Technology, University of Kuopio, Finland.
Pharm Res. 1994 Sep;11(9):1278-82. doi: 10.1023/a:1018938310628.
Timolol eyedrops may cause systemic side-effects in glaucoma patients due to absorption of the drug into systemic circulation. In a previous study, timolol concentrations in plasma were reduced if timolol was administered in ocular inserts instead of eyedrops. We compared the intraocular pressure lowering effect and systemic absorption of timolol inserts to those of 0.5% timolol eyedrops in humans. Inserts of silicone tubing released 90.3 +/- 13.9 micrograms of timolol in 24 hours in vivo. Timolol inserts afforded similar decreases in intraocular pressure in open-angle glaucoma patients as did b.i.d. eyedrops, but produced lower peak timolol concentrations in plasma, 0.70 +/- 0.10 ng/ml and 0.24 +/- 0.05 ng/ml, respectively. After eyedrops, peak concentrations were achieved at 15.0 +/- 2.2 min, while application of an insert resulted in a delayed peak (tmax = 623 +/- 195 min). The insert resulted in a higher systemically absorbed fraction of the timolol dose than the eyedrop, but the peak timolol concentration and daily absorbed amount of timolol were decreased. The release rate of timolol from the inserts in vivo was only slightly less than that in vitro. Silicone devices are useful for clinical testing of controlled delivery properties of ocular drugs.
噻吗洛尔滴眼液可能会因药物吸收进入全身循环而在青光眼患者中引起全身副作用。在先前的一项研究中，如果使用眼用插入剂而非滴眼液给药，血浆中的噻吗洛尔浓度会降低。我们比较了噻吗洛尔插入剂与人用0.5%噻吗洛尔滴眼液的降眼压效果及全身吸收情况。硅树脂管插入剂在体内24小时释放90.3±13.9微克噻吗洛尔。噻吗洛尔插入剂在开角型青光眼患者中降低眼压的效果与每日两次使用滴眼液相似，但血浆中噻吗洛尔的峰值浓度较低，分别为0.70±0.10纳克/毫升和0.24±0.05纳克/毫升。使用滴眼液后，在15.0±2.2分钟时达到峰值浓度，而使用插入剂则导致峰值延迟出现（达峰时间tmax = 623±195分钟）。与滴眼液相比，插入剂导致噻吗洛尔剂量的全身吸收分数更高，但噻吗洛尔的峰值浓度和每日吸收量降低。噻吗洛尔在体内从插入剂中的释放速率仅略低于体外释放速率。硅树脂装置可用于眼部药物控释特性的临床测试。
