TearClear, Princeton, NJ, USA.
Iuvo Bioscience, Rush, New York, USA.
J Ocul Pharmacol Ther. 2023 Nov;39(9):622-630. doi: 10.1089/jop.2023.0050. Epub 2023 Aug 15.
The systemic and ocular pharmacokinetics (PK), and ocular toxicity of benzalkonium chloride (BAK)-free TearClear latanoprost ophthalmic solution, 0.005% formulation (TC-002) were evaluated. TC-002 is designed to selectively capture BAK at the time of drug administration; therefore, the dose delivered to the eye contains no quantifiable level of preservative. The systemic and ocular PK of TC-002 were compared to a BAK containing reference listed drug (RLD, Xalatan™) over a 24-h period, after a single topical ocular dose to 1 eye of male Dutch Belted (DB) rabbits ( = 3/timepoint). Latanoprost acid concentrations were measured in plasma and ocular tissues. The ocular toxicity was evaluated in a separate study and included toxicokinetic evaluation of TC-002 after once daily topical ocular dosing into each eye of DB rabbits ( = 8/group) for at least 28 days. Toxicity endpoints included ophthalmic and clinical evaluations, necropsy, and microscopic evaluation of ocular tissues. Average ratios of values for TC-002/RLD ranged from 0.6 to 1.6, and and area under the concentration-time curve of last observed concentration (AUC) exposures to latanoprost acid were similar (<2-fold) between the 2 treatments. In the 28-day study, the was achieved in both groups in <0.5 h. There were no abnormal ocular findings. TC-002 with no quantifiable preservative or BAK-containing RLD exhibited similar ocular and systemic PK profiles. TC-002 was well tolerated and comparable to RLD. TC-002 retains the safety and PK characteristics of RLD without the added concern of long-term exposure of the eye to preservatives.
评价了无苯扎氯铵（BAK）的TearClear 拉坦前列素滴眼液（TC-002），0.005%制剂的全身和眼部药代动力学（PK）以及眼部毒性。TC-002 的设计目的是在药物给药时选择性地捕获 BAK；因此，递送至眼部的剂量不含可量化水平的防腐剂。在单次局部眼部给药后，将 TC-002 的全身和眼部 PK 与含有防腐剂的参比上市药物（RLD，Xalatan™）进行了比较，该药物给药于雄性荷兰兔（DB）的 1 只眼，共 3 只/时间点。在血浆和眼部组织中测量拉坦前列酸酸的浓度。在单独的研究中评估了眼部毒性，包括在 DB 兔的每只眼每日局部眼部给药 1 次后，TC-002 的毒代动力学评估（每组至少 28 天）。毒性终点包括眼科和临床评估、尸检以及眼部组织的显微镜评估。TC-002/RLD 值的平均比值范围为 0.6 至 1.6，拉坦前列酸酸的浓度-时间曲线最后观测浓度下的面积（AUC）暴露值相似（<2 倍）。在 28 天的研究中，两组均在 <0.5 小时内达到稳态。未观察到异常眼部发现。无定量防腐剂或含 BAK 的 RLD 的 TC-002 表现出相似的眼部和全身 PK 特征。TC-002 具有良好的耐受性，与 RLD 相当。TC-002 保留了 RLD 的安全性和 PK 特征，而无需长期担心防腐剂对眼睛的暴露。
