Distribution and metabolism of intravitreal cidofovir and cyclic HPMPC in rabbits

Abstract

The long retinal half-life observed presumably reflects formation of phosphorylated cidofovir within retinal cells. Cidofovir achieved a ten-fold higher level of phosphorylated drug in retina than cyclic HPMPC: Therefore, intravitreal cidofovir may be expected to suppress progression of retinitis for a longer period than an equivalent intravitreal dose of cyclic HPMPC: The intravitreal half-life of cidofovir was 20-fold longer than that of ganciclovir in the same animal model.

Characterization of a Novel Intraocular Drug-Delivery System Using Crystalline Lipid Antiviral Prodrugs of Ganciclovir and Cyclic Cidofovir

“…The estimated vitreous half-life for HDP-cCDV was 6.3 days, which favorably compares to 20 hours for CDV or 10 hours for cCDV. 12 The detected concentration at week 8 was 0.002 M, which is above the IC 50 for CMV. In this study, we did not detect HDP-cCDV in the retina, which could be due to low sensitivity of HPLC and fast conversion of HDP-cCDV into cCDV then into CDV by cellular phosphohydrolases.…”

Micelle formulation of hexadecyloxypropyl-cidofovir (HDP-CDV) as an intravitreal long-lasting delivery system

“…In this study, ex vivo drug release showed a half-life of 2.7 days which is quite a long vitreous half-life for a small molecule drug and supports formation of micelles in excised rabbit vitreous because similar small molecule drugs such as ganciclovir or cidofovir have vitreous half-lives of only hours [31, 32]. The current study did not perform an ex vivo release for CDV because its vitreous half-life was well characterized [32–34].…”

Intraocular Properties of Hexadecyloxypropyl–Cyclic-Cidofovir in Guinea Pigs

“…12 This means that to use those drugs intravitreally, frequent injections are needed. In contrast, HDP-cCDV has a much LU ET AL.…”