Effect of @entity57839 on the ocular disposition of a model substrate, XXXX .

@entity1855 @entity95 @entity57839 @entity1391 @entity5126 @entity1274 @entity941
PURPOSE: The objective of this study was to determine the effect of the multi-drug efflux transport protein, @entity57839 ( @entity57839 ), on the ocular distribution of a model substrate, @entity5126 . METHODS: Male New Zealand albino @entity95 (2-2.5 kg) were employed in these studies. Animals were kept under anesthesia and a concentric microdialysis probe was implanted in the vitreous humor and a linear probe in the anterior chamber. Isotonic @entity1391 buffered saline was perfused through the probes, and samples were collected every 20 minutes over a period of 10 hours. @entity5126 was administered both systemically (5 mg/kg bodyweight) and intravitreally (5.68 microg and 0.568 microg). Inhibition experiments were performed in vivo in the presence of @entity1855 , which is a known @entity57839 inhibitor. RESULTS: Vitreal pharmacokinetic parameters of @entity5126 in the presence of @entity1855 , i.e., Area under the curve (AUC) (39.27 +/- 6.47 min. microg/ml), maximum concentration achieved (Cmax) (0.095 +/- 0.011 microg/ml), vitreal elimination half-life (231.96 +/- 10.77 min), vitreal permeation half-life (16.57 +/- 6.96 min) were significantly different from the control values (19.21 +/- 3.73 min. microg/ml, 0.05 +/- 0.008 microg/ml, 165.08 +/- 31.5 min, 43.29 +/- 12.5 min respectively). A significant elevation in anterior chamber Cmax and AUC was also observed in the presence of @entity1855 . @entity1855 had no significant effect on vitreal kinetics of @entity5126 following intravitreal dose of 5.68 micro g, but a significant difference was observed at a lower dose of @entity5126 (0.568 microg). A decrease in vitreal elimination half-life and AUC was observed in the presence of @entity1855 relative to control. Ocular kinetics of @entity941 was studied to ascertain ocular barrier integrity in the presence of @entity1855 . Western-blot analysis of retina-choroid sections indicates expression of @entity57839 on @entity95 retina-choroid. CONCLUSION: Results suggest the involvement of a multi drug efflux transporter on the retinal pigment epithelium and @entity1274 affecting the intraocular kinetics of its substrates following systemic and intravitreal administrations.
