PHARMACOKINETICS AND RETINAL TOXICITY OF INTRAVITREAL LIPOSOME-ENCAPSULATED 5-FLUOROURIDINE

Background: Fluoropyrimidines may be effective in preventing prolifera tive vitreoretinopathy after repair of complicated retinal detachments . Liposome encapsulation of these antiproliferative drugs may extend t he intravitreal half-life and increase their efficacy. Methods: The cu rrent study evaluated the pharmacokinetic behavior of intravitreally i njected 5-fluorouridine (5-FUR), free and encapsulated in liposomes, e ither conventionally or coated with collagen into 25 New Zealand rabbi ts. Additionally, we investigated the retinal toxicity of intravitreal injections of 100, 250 and 500 mu g as well as 1 mg 5-FUR as free dru g or encapsulated in liposomes in the rabbit eye. Results: The half-li fe of free 5-FUR after liposome injection into the vitreous cavity was 18.17 +/- 2.43 h, considerably longer than the half-life of free 5-FU R (0.82 h). Electrophysiologic tests did not show any changes in laten cy and a-wave amplitude and minimal changes in the b-wave amplitude. H istopathologic studies revealed integrity of the inner limiting membra ne, and mild vacuolization in the outer retina. Conclusion: Encapsulat ion of 5-FUR within liposomes markedly increases its intravitreal half -life. Our study suggests that liposome-encapsulated 5-FUR is not toxi c to the retina even at doses of 1 mg.