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Pharm Res. 2002 Aug;19(8):1194-202.
Mechanism of corneal permeation of L-valyl ester of acyclovir: targeting the oligopeptide transporter on the rabbit cornea.

Anand BS, Mitra AK.

Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 64110-2499, USA.

PURPOSE: To delineate mechanisms associated with the corneal transport of a L-valine prodrug of an antiviral agent, acyclovir. METHOD: The permeability and enzymatic hydrolysis of L-Val-ACV were evaluated using freshly excised rabbit cornea. Transport mechanism across rabbit cornea was investigated through a competitive inhibition study of L-Val-ACV with other substrates of human peptide transporter (hPepT1). RESULTS: L-Valyl ester of Acyclovir (L-Val-ACV) was approximately threefold more permeable across the intact rabbit cornea than acyclovir (ACV). Dipeptides, beta-lactam antibiotics, and angiotensin converting enzyme (ACE) inhibitors, strongly inhibited the transport of L-Val-ACV indicating that a carrier mediated transport system specific for peptides is primarily responsible for the corneal permeation of L-Val-ACV. L-Val-ACV transport was found to be saturable (Km = 2.26 +/- 0.34 mM, Jmax = 1.087 +/- 0.05 nmoles cm(-2) min(-1)), energy and pH dependent. CONCLUSIONS Functional evidence of an oligopeptide transport system present on the rabbit cornea has been established. The peptide transporter on the corneal epithelium may be targeted to improve the ocular bioavailability of poorly absorbed drugs.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12240946&dopt=Abstract

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