In vitro corneal permeation of unoprostone isopropyl (UI) and its metabolism in the isolated pig eye

Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
M BabioleC Schoch

Abstract

The corneal permeability, hydrolysis, and metabolism of unoprostone isopropyl (UI), a docosanoid, were examined in isolated porcine ocular tissues. The apparent permeability coefficient (Papp) of the esterified prodrug and of the acid metabolite were determined in a modified Valia-Chien permeation chamber and quantified by high performance liquid chromatography. Enzymatic hydrolysis and subsequent metabolism were examined in isolated tissue homogenates. The prodrug (ester form) was found to permeate the isolated intact porcine cornea with a Papp of 9.47 x 10(-7) cm/sec. Only the acid metabolite could be detected in the receiver chamber, indicating the requirement of hydrolysis for permeation. The acid metabolite could not permeate the intact cornea but was able to cross an epithelium-denuded cornea with a Papp of 1.22 x 10(-6) cm/sec. Enzymatic hydrolysis of UI was confined to the isolated intact cornea and epithelium, indicating that the esterase activity was localized in the corneal epithelium. Incubations with different porcine ocular tissues, conjunctiva, iris-ciliary body, trabeculum, as well as aqueous humor, did not reveal other metabolites. These findings demonstrate that the ocular penetration of UI is dependent on its...Continue Reading

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Citations

Mar 24, 2005·Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft·L MeyerS Reichl
Oct 25, 2003·Progress in Retinal and Eye Research·Vital P CostaLuis Metzner Serra
Jun 14, 2003·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Sigrid KnappUwe Pleyer
May 22, 2009·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·John J ArnoldPratap Challa
Oct 9, 2007·Journal of Pharmaceutical Sciences·Yoshihisa Shirasaki
Nov 6, 2009·Journal of Pharmaceutical Sciences·Soumyajit MajumdarRamesh Srirangam
Jan 15, 2016·Drug Delivery and Translational Research·Priyanka Agarwal, Ilva D Rupenthal
Aug 2, 2011·Theriogenology·S E Gillard KingmaT S Chenier
Oct 28, 2005·Current Eye Research·Jiro NumagaMakoto Araie

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