Non-Oral Formulations (R&D), Sun Pharma Advanced Research Company Ltd, Vadodara, India.
Curr Eye Res. 2021 Jul;46(7):1031-1037. doi: 10.1080/02713683.2020.1855660. Epub 2021 Mar 15.
: Many intraocular pressure (IOP)-lowering medications contain benzalkonium chloride (BAK), a preservative associated with unfavorable outcomes.A formulation of latanoprost 0.005% ophthalmic without BAK is approved by the FDA and indicated for reduction of IOP in patients with open-angle glaucoma or ocular hypertension. We present two preclinical studies of latanoprost 0.005% BAK-free vs latanoprost with BAK; one examining plasma and ocular tissue pharmacokinetics (PK) in New Zealand white rabbits, and one comparing in vivo IOP-lowering efficacy in healthy beagles.: In the PK study, one drop of treatment (latanoprost BAK-free or latanoprost with BAK) was instilled into both eyes of rabbits in each treatment group (n = 18). At 0.25, 0.5, 1, 4, 6, and 24 hours postdose, three rabbits per study group underwent terminal blood and tissue collection.In the IOP study, in the first dosing period, both eyes of each beagle received either 1 drop latanoprost BAK-free or latanoprost with BAK, once daily for 10 days. After a 10-day washout period, a second 10-day dosing period was conducted and latanoprost BAK-free or latanoprost with BAK were dosed in the opposite eyes, respectively. IOP measurements were taken at 1, 6, and 12 hours postdose.: The maximum plasma concentration for latanoprost BAK-free and latanoprost with BAK occurred 0.25 hours after administration (174.1 vs 217.2 pg/mL, respectively). Area under the concentration time curve from zero to infinity was highest in aqueous humor for latanoprost BAK-free and latanoprost with BAK (133.1 vs 119.6 hr·ng/mL, respectively) and was not estimable in vitreous humor. In beagles, once-daily administration of latanoprost BAK-free or latanoprost with BAK led to a significant reduction in IOP vs baseline ( < .001); there was no difference between groups ( > .05).: Latanoprost BAK-free showed comparable activity in reducing IOP, and comparable plasma and ocular PK parameters to latanoprost with BAK.
: 许多降眼压药物（IOP）含有苯扎氯铵（BAK），这是一种与不良结果相关的防腐剂。一种不含 BAK 的拉坦前列素 0.005%的滴眼剂已获得 FDA 批准，用于降低开角型青光眼或高眼压症患者的 IOP。我们进行了两项关于不含 BAK 的拉坦前列素 0.005%与含 BAK 的拉坦前列素的临床前研究；一项研究检查了新西兰白兔的血浆和眼部组织药代动力学（PK），另一项研究比较了健康比格犬的体内降低 IOP 的效果。：在 PK 研究中，每组（n=18）的每只兔子的双眼滴一滴治疗药物（不含 BAK 的拉坦前列素或含 BAK 的拉坦前列素）。在给药后 0.25、0.5、1、4、6 和 24 小时，每组三只兔子进行终末血液和组织采集。在 IOP 研究中，在第一个给药期，每只比格犬的双眼每天接受一滴不含 BAK 的拉坦前列素或含 BAK 的拉坦前列素，连续给药 10 天。在 10 天的洗脱期后，进行第二个 10 天的给药期，分别在双眼滴注不含 BAK 的拉坦前列素或含 BAK 的拉坦前列素。给药后 1、6 和 12 小时测量 IOP。：不含 BAK 的拉坦前列素和含 BAK 的拉坦前列素的最大血浆浓度分别在给药后 0.25 小时达到（分别为 174.1 和 217.2 pg/mL）。从零到无穷大的浓度时间曲线下面积在不含 BAK 的拉坦前列素和含 BAK 的拉坦前列素的房水中最高（分别为 133.1 和 119.6 hr·ng/mL），在玻璃体液中无法估计。在比格犬中，每天一次给药不含 BAK 的拉坦前列素或含 BAK 的拉坦前列素可显著降低 IOP（<0.001）；两组之间无差异（>0.05）。：不含 BAK 的拉坦前列素在降低 IOP 方面具有相当的活性，并且在血浆和眼部 PK 参数方面与含 BAK 的拉坦前列素相当。
