Comparison of In Vitro Corneal Permeation and In Vivo Ocular Bioavailability in Rabbits of Three Marketed Latanoprost Formulations.

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Laure Chauchat, Camille Guerin, Yulia Kaluzhny, Jean-Paul Renard
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引用次数: 0

Abstract

Background and objective: All latanoprost formulations currently available for the treatment of glaucoma or ocular hypertension contain the same concentration of latanoprost (0.005%) but differ in excipients, which may affect corneal drug permeability or stability. This study aimed at comparing corneal penetration of three marketed latanoprost solutions with different excipient formulations in in vitro and in vivo drug permeability studies.

Methods: Three latanoprost formulations were tested under good laboratory practice conditions: a formulation containing benzalkonium chloride (BAK) but no surfactant (Preserved latanoprost); the same formulation except preservative-free (PF) without BAK or surfactant (SF) (PF SF latanoprost); and a different formulation without BAK but containing a non-ionic surfactant (MGHS 40 at 5%) combined with thickening agents (Carbomer 974P, Macrogol 4000) (PF latanoprost). Corneal permeation of latanoprost acid (LAT) was first determined in vitro using a reconstructed human corneal epithelium tissue. Then, in vivo pharmacokinetic studies were performed on pigmented rabbits, for which LAT concentration was measured in the aqueous humour (AH) and iris-ciliary body (ICB).

Results: In vitro, the cumulative transport of LAT was linear between 1 h and 4 h for preserved latanoprost and PF SF latanoprost, and LAT concentrations matched exactly at each timepoint. By contrast, the permeation of PF latanoprost was linear between 2 h and 12 h and was significantly lower than that of preserved latanoprost and PF SF latanoprost at 4 and 8 h (p < 0.001). In rabbits, the concentrations of LAT in AH and ICB were not statistically different between preserved latanoprost and PF SF latanoprost at each timepoint, except at 1 h in ICB (p = 0.005). By comparison, the LAT concentration of PF latanoprost was statistically (p < 0.05) lower than that of preserved latanoprost and PF SF latanoprost in AH and ICB from 0.5 to 3 h.

Conclusion: BAK did not influence the corneal penetration of latanoprost in in vitro and in vivo studies. The formulation containing a non-ionic surfactant resulted in lower and slower ocular penetration compared with preserved or PF SF formulations. This raises questions about the relevance of BAK and some surfactants in enhancing corneal penetration of ocular formulations.

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三种市售拉坦前列素制剂在兔体内角膜渗透性和体内眼生物利用度的比较。
背景和目的:目前可用于治疗青光眼或高眼压的所有拉坦前列素制剂都含有相同浓度(0.005%)的拉坦前列肽,但赋形剂不同,这可能会影响角膜药物的渗透性或稳定性。本研究旨在比较三种市售拉坦前列素溶液与不同赋形剂配方在体外和体内药物渗透性研究中的角膜渗透性。方法:在良好的实验室操作条件下测试三种拉坦前列素制剂:一种含有苯扎氯铵(BAK)但不含表面活性剂的制剂(保存的拉坦前列肽);除了不含BAK或表面活性剂(SF)的无防腐剂(PF)(PF-SF拉坦前列素)之外的相同制剂;以及不含BAK但含有非离子表面活性剂(MGHS 40,5%)与增稠剂(Carbomer 974P,Macrogol 4000)(PF拉坦前列素)的不同制剂。拉坦前列素酸(LAT)的角膜渗透首先在体外使用重建的人角膜上皮组织进行测定。然后,对色素兔进行体内药代动力学研究,测量房水(AH)和虹膜睫状体(ICB)中LAT的浓度。相比之下PF-拉坦前列素的渗透在2小时和12小时之间是线性的,并且在4小时和8小时时显著低于保存的拉坦前列素和PF-SF-latanoprost(p结论:在体外和体内研究中,BAK不影响拉坦前列素的角膜穿透力。与保存的或PF-SF制剂相比,含有非离子表面活性剂的制剂导致更低和更慢的眼部穿透力。这引发了人们对BAK和一些表面活性剂在增强眼部制剂的角膜穿透性方面的相关性的质疑。
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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
64
审稿时长
>12 weeks
期刊介绍: Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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