EFFECT OF PARTIAL RETINAL DESTRUCTION AND GLIOSIS ON THE INTRAVITREALPHARMACOKINETICS OF HPMPC

Purpose: Intravitreal HPMPC ([S]-1-[3-hydroxy-2 phosphonylmethoxypropy l cytosine) has a long antiviral effect in patients with cytomegalovir us retinitis. The authors evaluated the pharmacokinetics of intravitre al injections of HPMPC to understand major route of HPMPC elimination in a pigmented rabbit that had undergone scatter laser photocoagulatio n over half of the retinal surface. Methods: The authors treated the i nferior half of the retina, receiving an average of 605 grade 3 or 4 ( gray-white or white) diode laser burns in a scatter fashion in the lef t eyes of 13 rabbits. After 4 weeks, 13 rabbits received intravitreal injection of HPMPC (100 mu g in 0.1 mL) in both eyes. Forty-eight hour s after injection, unfixed vitreous samples were obtained for high-pre ssure liquid chromatography analysis. Two rabbits were used for light microscopic examination of diode laser photocoagulated retina with the perfusion fixation. Results: The HPMPC concentration in the vitreous was 5.93 +/- 1.75 mu g/mL in the laser-treated group and 4.76 +/- 1.2 mu g/mL in the control group 48 hours after intravitreal HPMPC injecti on. The difference was statistically different (P = 0.037). Conclusion s: Results showed a higher concentration of intravitreal HPMPC in the eye that had approximately 25% of the retina destroyed by the laser ph otocoagulation. The higher concentration is likely the result of reduc ed elimination and a concomitant increase in half-life. This suggests that HPMPC may be eliminated via the retinal route. Eyes with more ext ensive retinal involvement with human cytomegalovirus may have an even longer duration of action of intravitreal HPMPC. This may lead to mod ification of dosing regimens.