Transport of cidofovir across the pigmented rabbit conjunctiva

Purpose. (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (Cidofovir) is an acyclic nucleotide analog that is effective against opportunistic ocular infections caused by adeno- and herpes viruses. The aim of this study was to delineate its transport characteristics in the pigmented rabbit conjunctiva. Method. The excised pigmented rabbit conjunctiva was mounted in the modified Ussing chamber. Cidofovir flux study was initiated by applying 3H-Cidofovir in the donor chamber. Cidofovir in the receiver sample and mounted tissue was measured by assaying ³H-Cidofovir in the liquid scintillation counter. Results. Cidofovir flux and tissue accumulation in the mucosal to serosal (M->S) direction proportionally increased with increasing concentration of cidofovir up to 1 mM. Apparent permeability coefficient (Papp) and tissue accumulation in the M->S direction were 2-fold higher than these in the opposite direction (p < 0.05). Papp and tissue accumulation in the M->S direction was significantly inhibited by 76% and 95%, respectively at 4°C (p < 0.01). 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS, an anion-transport inhibitor, 0.2 mM) inhibited Papp and accumulation in the M->S direction by 88% and 98%, respectively (p < 0.01). Conclusion. Cidofovir transport across conjunctiva may be mediated by an anion sensitive membrane protein.