Novagali Pharma, Evry, France.
J Ocul Pharmacol Ther. 2012 Oct;28(5):515-23. doi: 10.1089/jop.2011.0245. Epub 2012 Jun 6.
Benzalkonium chloride (BAK), a common preservative in eye drops, can induce ocular surface toxicity that may decrease glaucoma therapy compliance. The ocular hypotensive effect, pharmacokinetic (PK) profiles, and local tolerance of a preservative-free latanoprost 0.005% cationic emulsion (Catioprost(®)), and a BAK-preserved latanoprost 0.005% solution (Xalatan(®)), were compared.
The ocular hypotensive effect was evaluated in monkeys with elevated intraocular pressure (IOP) induced by laser photocoagulation of the trabecular meshwork. Each monkey (n=8) received both latanoprost formulations once daily for 5 consecutive treatment days in a crossover design with at least a 2-week washout period between treatments. IOP was measured at baseline (on day 1, no instillation), on vehicle treatment day (day 0), and on treatment days 1, 3, and 5 before drug instillation and then hourly for 6 h. In rabbits, the ocular and systemic concentrations of latanoprost free acid were determined following a single instillation and the local tolerance of twice daily instillations over 28 days was assessed.
Both the preservative-free and BAK-preserved latanoprost formulations shared the same efficacy profile with the maximum IOP reduction occurring 2 h after each morning dose (-15%, -20%, and -26%; -15%, -23%, and -23% on days 1, 3, and 5, respectively) and lasting through 24 h. The equivalence in efficacy was confirmed by the PK data demonstrating similar area under the curves (AUCs). While both formulations were well tolerated, the incidence of conjunctival hyperemia was reduced by 42% with the BAK-free latanoprost cationic emulsion.
In animal models, a preservative-free latanoprost cationic emulsion was as effective as Xalatan(®) for lowering IOP with an improved ocular tolerance profile.
苯扎氯铵（BAK）是一种常用于滴眼剂的防腐剂，可引起眼表毒性，从而降低青光眼治疗的依从性。本研究比较了一种不含防腐剂的拉坦前列素 0.005%阳离子乳液（Catioprost(®)）和含防腐剂的拉坦前列素 0.005%溶液（Xalatan(®)）的降眼压作用、药代动力学（PK）特征和局部耐受性。
通过激光光凝小梁网将猴子的眼内压（IOP）升高来评估降眼压作用。每只猴子（n=8）均以交叉设计接受两种拉坦前列素制剂，连续 5 天，每天 1 次，每种制剂之间至少间隔 2 周洗脱期。在基线（第 1 天，无滴注）、载体处理日（第 0 天）以及治疗日 1、3 和 5 滴注前测量 IOP，然后在滴注后每小时测量 6 小时。在兔子中，单次滴注后测定拉坦前列素游离酸的眼内和全身浓度，并评估每天 2 次滴注 28 天的局部耐受性。
两种拉坦前列素制剂均具有相同的疗效特征，最大眼压降低发生在每天早晨剂量后 2 小时（第 1、3 和 5 天分别为-15%、-20%和-26%；-15%、-23%和-23%），持续 24 小时。PK 数据证实了等效性，表明 AUC 相似。两种制剂均耐受良好，但与含防腐剂的拉坦前列素溶液相比，不含防腐剂的拉坦前列素阳离子乳液使结膜充血的发生率降低了 42%。
在动物模型中，一种不含防腐剂的拉坦前列素阳离子乳液与 Xalatan(®)降低 IOP 的效果相同，但眼部耐受性更好。
