Zhang Li, Zhang Junjie, Wang Liya, Xia Huiyun
Henan Eye Institute, No. 7 Weiwu Road, Zhengzhou, Henan Province 450003, China.
Curr Eye Res. 2009 Apr;34(4):257-63. doi: 10.1080/02713680902725962.
To evaluate the ocular pharmacokinetics and availability of baicalein following topical application.
Hydroxypropyl beta-cyclodextrin (HP-beta -CD) was used to formulate an aqueous eye drop to improve aqueous solubility of baicalein. A single dose of either baicalein suspension (1%) (Bai-SP) or baicalein (1%)/HP-beta-CD (10%) solution (Bai-CD) was topically applied to rabbits. Aqueous humor and cornea were collected after 5, 10, 20, 30, 45, 60, 90, and 120 min. Baicalein concentrations were determined by high-performance liquid chromatography (HPLC) after extraction.
After topically applying Bai-CD, the baicalein concentrations in aqueous humor were significantly increased at 20-120 min except at 90 min compared with those of Bai-SP (p < 0.05). The highest levels of baicalein in aqueous humor (Cmax, 4.11 +/- 0.75 microg/ml) were obtained after 30 min application of Bai-CD, 3.6 times greater than that corresponding to the Bai-SP at 20 min. The Bai-CD produced an over 2.1-fold bioavailability (AUC(0-120), area under the concentration time curve between 0 and 120 min) increase in aqueous humor compared to the Bai-SP. Peak baicalein concentration in cornea (56.53 +/- 17.02 microg/g) was achieved within 5 min after topical application of Bai-CD and 4.5 times higher than that of Bai-SP at the same timepoint. The baicalein levels in corneas obtained after application of Bai-CD were all much higher than those obtained by Bai-SP (p < 0.01), whereas the drug levels became undetectable 30 min after topical application of Bai-SP.
Bai-CD formulation is superior to Bai-SP for increasing ocular bioavailability.
评估局部应用后黄芩苷的眼内药代动力学及可用性。
使用羟丙基-β-环糊精（HP-β-CD）配制水性滴眼液以提高黄芩苷的水溶性。将单剂量的黄芩苷混悬液（1%）（Bai-SP）或黄芩苷（1%）/HP-β-CD（10%）溶液（Bai-CD）局部应用于兔眼。在5、10、20、30、45、60、90和120分钟后收集房水和角膜。提取后通过高效液相色谱法（HPLC）测定黄芩苷浓度。
局部应用Bai-CD后，与Bai-SP相比，房水中黄芩苷浓度在20 - 120分钟时显著升高（90分钟除外）（p < 0.05）。局部应用Bai-CD 30分钟后房水中黄芩苷达到最高水平（Cmax，4.11±0.75μg/ml），比Bai-SP在20分钟时相应值高3.6倍。与Bai-SP相比，Bai-CD使房水中的生物利用度（AUC(0 - 120)，0至120分钟浓度-时间曲线下面积）提高了2.1倍以上。局部应用Bai-CD后5分钟内角膜中黄芩苷达到峰值浓度（56.53±1- 02μg/g），比同一时间点的Bai-SP高4.5倍。应用Bai-CD后角膜中的黄芩苷水平均远高于Bai-SP（p < 0.01），而局部应用Bai-SP 30分钟后药物水平无法检测到。
Bai-CD制剂在提高眼内生物利用度方面优于Bai-SP。
