Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Lab, Beijing, China.
Retina. 2012 Nov-Dec;32(10):2158-64. doi: 10.1097/IAE.0b013e3182576d1d.
To investigate the concentrations and pharmacokinetics of ketorolac in the rabbits by three different routes of administrations: a single intracameral, intravitreal, and suprachoroidal injection.
Fifty-four New Zealand white rabbits received ketorolac (250 μg/0.05 mL) in one eye by a single intracameral injection (group A, n = 18), single intravitreal injection (group B, n = 18), and single suprachoroidal injection (group C, n = 18). Drug concentrations in the vitreous, retina-choroid (RC), and plasma were determined by the methods of high-performance liquid chromatography at 0.5, 1, 2, 4, 8, and 24 hours after injection. The concentrations in the opposite eyes were also investigated.
The mean maximum concentrations (Cmax) of ketorolac in the vitreous and RC were 0.378 ± 0.19 μg/mL and 3.15 ± 0.49 μg/g (at 0.5 hours), respectively, in group A; 156.2 ± 20.74 μg/mL (at 0.5 hours) and 208.0 ± 21.67 μg/g (at 1 hours), respectively, in group B; and 0.873 ± 0.34 μg/mL and 56.71 ± 22.64 μg/g (at 0.5 hours), respectively, in group C. In the RC, the area under the curve (AUC0-t) in group B (866.1 ± 52.67 μg/g·h) was higher (P < 0.01) than that in group C (77.10 ± 25.90 μg/g·h). The elimination half-life (t1/2) in group B (3.09 hours) was longer (P < 0.01) than that in group C (1.19 hours). In the control eyes, a drug level below 2 μg/g was detected in the RC in group C. Plasma concentrations were below 0.4 μg/mL in all 3 groups. Ketorolac was detectable in the RC till 24 hours after the intravitreal injection and 8 hours after the suprachoroidal injection.
Intravitreal injection of ketorolac produced higher intraocular drug concentrations for a longer period compared with the other two routes. Suprachoroidal injection of ketorolac could reach an effective drug level in the RC with short half-lives and low drug levels in the vitreous. The plasma drug concentrations were low by all three routes.
通过三种不同途径（单次前房内、玻璃体内和脉络膜上腔注射）研究单次给予兔酮咯酸的浓度和药代动力学。
54 只新西兰白兔的一只眼接受单次前房内注射（A 组，n = 18）、单次玻璃体内注射（B 组，n = 18）和单次脉络膜上腔注射（C 组，n = 18）酮咯酸（250μg/0.05mL）。在注射后 0.5、1、2、4、8 和 24 小时通过高效液相色谱法测定玻璃体内、视网膜脉络膜（RC）和血浆中的药物浓度。同时也检测了对侧眼的药物浓度。
A 组兔玻璃体内和 RC 的最大浓度（Cmax）分别为 0.378 ± 0.19μg/mL（0.5 小时）和 3.15 ± 0.49μg/g（0.5 小时）；B 组兔玻璃体内和 RC 的 Cmax 分别为 156.2 ± 20.74μg/mL（0.5 小时）和 208.0 ± 21.67μg/g（1 小时）；C 组兔玻璃体内和 RC 的 Cmax 分别为 0.873 ± 0.34μg/mL（0.5 小时）和 56.71 ± 22.64μg/g（0.5 小时）。在 RC 中，B 组的曲线下面积（AUC0-t）（866.1 ± 52.67μg/g·h）高于 C 组（77.10 ± 25.90μg/g·h）（P<0.01）。B 组的消除半衰期（t1/2）（3.09 小时）长于 C 组（1.19 小时）（P<0.01）。在对照组眼中，C 组的 RC 中检测到的药物浓度低于 2μg/g。三组的血浆浓度均低于 0.4μg/mL。玻璃体内注射后，酮咯酸在 RC 中可检测到 24 小时，脉络膜上腔注射后 8 小时。
与其他两种途径相比，玻璃体内注射酮咯酸可产生更高的眼内药物浓度并维持更长时间。脉络膜上腔注射酮咯酸可在短半衰期和低玻璃体药物浓度的情况下达到有效的 RC 药物水平。三种途径的血浆药物浓度均较低。
