Shafiee Afshin, Bowman Lyle M, Hou Eddie, Hosseini Kamran
InSite Vision, Alameda, CA, USA.
Clin Ophthalmol. 2013;7:1549-56. doi: 10.2147/OPTH.S48766. Epub 2013 Jul 31.
To compare the aqueous humor (AH) and iris-ciliary body (ICB) concentration of bimatoprost in rabbit eyes treated with ISV-215 (0.03% bimatoprost formulated in DuraSite) with the marketed product bimatoprost 0.03% ophthalmic solution.
The left eye of rabbits received a single topical instillation of either ISV-215 (n = 32 eyes) or bimatoprost 0.03% (n = 32 eyes). At predetermined time points, levels of bimatoprost and bimatoprost acid in the AH and the ICB were quantified by HPLC-MS/MS.
Both bimatoprost and bimatoprost acid were detected in the AH and the ICB within 15 minutes of dosing. Bimatoprost acid concentrations in both compartments were markedly higher than bimatoprost. There was a statistically significant (P < 0.01) increase in the concentration of the prodrug in the AH and its acid form in the ICB in animals treated with ISV-215 compared to bimatoprost 0.03%. In the ISV-215-treated rabbit eyes, the highest concentrations of bimatoprost and bimatoprost acid were in the ICB and AH, respectively, while in the bimatoprost 0.03%-treated eyes, no differences in the drug content of the selected ocular tissues were observed.
Bimatoprost 0.03% formulated in DuraSite has superior ocular distribution and area under the curve compared to bimatoprost 0.03% in rabbit eyes. This improvement in the pharmacokinetic parameters of ISV-215 may provide us with a better platform to optimize a bimatoprost formulation that offers the same degree of efficacy in lowering intraocular pressure and improved therapeutic index in glaucomatous patients by lessening the ocular side effects associated with long-term use of topical prostaglandin F2α analogs.
比较用ISV - 215（0.03%比马前列素制成的DuraSite制剂）治疗的兔眼与市售产品0.03%比马前列素滴眼液中比马前列素在房水（AH）和虹膜睫状体（ICB）中的浓度。
兔的左眼单次局部滴注ISV - 215（n = 32只眼）或0.03%比马前列素（n = 32只眼）。在预定时间点，通过高效液相色谱 - 串联质谱法（HPLC - MS/MS）对AH和ICB中比马前列素和比马前列素酸的水平进行定量。
给药后15分钟内，在AH和ICB中均检测到比马前列素和比马前列素酸。两个腔室中的比马前列素酸浓度均明显高于比马前列素。与0.03%比马前列素相比，用ISV - 215治疗的动物房水中前药浓度及其在ICB中的酸形式浓度有统计学显著升高（P < 0.01）。在经ISV - 215治疗的兔眼中，比马前列素和比马前列素酸的最高浓度分别在ICB和AH中，而在0.03%比马前列素治疗的眼中，未观察到所选眼组织中药物含量的差异。
与兔眼中的0.03%比马前列素相比，制成DuraSite制剂的0.03%比马前列素具有更好的眼部分布和曲线下面积。ISV - 215药代动力学参数的这种改善可能为我们提供一个更好的平台，以优化比马前列素制剂，通过减少与长期使用局部前列腺素F2α类似物相关的眼部副作用，在降低青光眼患者眼压方面提供相同程度的疗效并改善治疗指数。
