A pharmacokinetic model of intravitreal delivery of ganciclovir.
A pharmacokinetic model of intravitreal drug delivery was developed for describing the elimination and distribution of ganciclovir in the eye following intravitreous polymeric delivery. The model was based on Fick's second law of diffusion and assumed a cylindrical vitreous body. The model parameters such as the diffusion coefficient and the partition coefficient of the drug in the vitreous body and its surrounding tissues were determined from in vitro experiments using rabbit tissues. The time course of in vivo mean concentration of ganciclovir in the rabbit vitreous body agreed well with the profile calculated from the present pharmacokinetic model for both membrane-controlled polymeric devices and biodegradable rod-matrix systems. The clinical vitreous concentration following implantation of the membrane-controlled delivery system was the same order of magnitude but approximately four times lower than that predicted from the present model. This may indicate the metabolism of ganciclovir and/or the facilitated transport across the retina/choroid membrane in the human eye.
Tojo
K
K
Kyushu Institute of Technology, Fukuoka, Japan. tojo@bse.kyutech.ac.jp
Nakagawa
K
K
Morita
Y
Y
Ohtori
A
A
D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D015774:Ganciclovir / Q000493:pharmacokinetics*; D006801:Humans; D008954:Models, Biological; D011817:Rabbits; D014822:Vitreous Body / Q000378:metabolism*
D000998:Antiviral Agents; D015774:Ganciclovir