Pharmacokinetics of the fluocinolone/5-fluorouracil codrug in the gas-filled eye

Purpose: To determine the effect of intraocular gas tamponade on drug level s achieved with the intravitreal sustained-release fluocinolone (FL)/5-fluo rouracil (5-FU) codrug pellet. Methods: After insertion of a 10-mg codrug pellet into the right eyes of 43 New Zealand white rabbits, perfluoropropane (0.4 mL of 100% C3F8) or a con trol sham was then injected into the midvitreous cavity. On postoperative d ays 2, 4, 7, 21, and 42, aqueous samples were collected, the rabbits were k illed, and the right eyes were enucleated, The vitreous and remaining codru g pellet were then isolated. Pellet and intravitreal drug levels were deter mined by high-pressure liquid chromatography. Results: No measurable drug levels were detected in any of the aqueous samp les. Maximal gas expansion occurred by day 4 and partial resorption was obs erved by days 14 to 21. Vitreous FL and 5-FU levels during C3F8 expansion ( day 2) were statistically significantly higher in the gas-filled eyes. On p ostoperative days 4, 7, 21, and 42, there were no statistically significant differences between FL and 5-FU drug levels in eyes containing C3F8 as com pared with control eyes. Pellet codrug, FL, and 5-FU levels over time were similar in gas-filled and control eyes, Conclusions: Intraocular gas tamponade does not significantly affect the su stained intravitreal drug levels achieved with the FL/5-FU codrug. If clini cally efficacious, the FL/5-FU codrug formulation does not need to be alter ed to treat proliferative vitreoretinopathy in the presence of intraocular gas.