Purchase this article with an account.
BS Anand, AK Mitra; Evidence for the Presence of an Oligopeptide Transport System on the Rabbit Cornea: Interactions of a Nonpeptidic Drug, Valcyclovir, with the Oligopeptide Transporter . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3251.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: To characterize the presence of an oligopeptide transporter on the Corneal Epithelium and to determine the aqueous stability, ocular tissue hydrolysis of L-valyl ester of Acyclovir (VACV). Methods: The aqueous stability of L-valine ester prodrug of Acyclovir (VACV) was estimated in buffers ranging from 1.2-9.0. Tissue hydrolysis studies were performed using ocular tissue homogenates from the male New Zealand albino rabbits. Transport studies using Side-Bi-SideTM diffusion cells were performed across intact rabbit cornea. Results: The pH of maximal stability was found out to be 4.2. Tissue hydrolysis rate constants were determined to be: cornea- 0.0081(±0.0012), aqueous humor- 0.026(±0.0034), lens- 0.011(±0.00038), iris-ciliary- 0.28(±0.019), vitreous humor- 0.0071(±0.00089) and retina-choroid- 0.108(±0.014) - min-1 mg-1 protein. The permeability of VACV across cornea was found to be approximately 2.5 fold higher than that of ACV. The transport of VACV in presence of captopril, enalapril cephalexin, Cephazolin and glycylsarcosine was inhibited significantly (p<0.05). The permeability of cephalexin in presence of glycyl-sarcosine was found to be approximately 6.5 fold less than that of cephalexin (control). The transport of VACV was found to be saturable and pH dependent. Moreover the transport of [3H] glycylsarcosine was also inhibited in presence of 10mm glycylsarcosine. Conclusion: VACV is very soluble as compared to ACV. The prodrug is readily converted in the ocular tissues to yield the parent drug ACV. Permeability values of VACV in presence of various PEPT substrates indicate the presence of a peptide transport system on the corneal epithelium. Transport of VACV is saturable at higher concentrations and pH dependent, which is characteristic of an H+ coupled oligopeptide transport system. The presence of an oligopeptide transport system on the Corneal epithelium could be utilized to deliver peptidomimetics across the Corneal epithelium to cure ocular infections. Acknowledgements: Glaxo Wellcome for the generous supply of L-valine-ACV and NEI grants EY 09171 and EY 10659.
This PDF is available to Subscribers Only