IN-VIVO IN-VITRO CORRELATION OF INTRAVITREAL DELIVERY OF DRUGS WITH THE HELP OF COMPUTER-SIMULATION

The elimination of dexamethasone sodium m-sulfobenzoate, DMSB, followi ng intravitreal injection, was measured in rabbit vitreous body under in vivo and is vitro conditions. The rate of elimination in vivo was a ppreciably greater than that ill vitro, indicating that the in vivo da ta include not only the elimination due to metabolism/degradation in t he vitreous humor, but also the elimination through the surrounding ti ssues such as the posterior aqueous humor, the retina/choroid/sclera m embrane, and the lens. A general mathematical model based on Fick's se cond law of diffusion was developed for describing the pharmacokinetic s of the intravitreal injection of DMSB. The model parameters were ind ependently determined from a set of in vitro experiments. The in vivo data of elimination of DMSB following intravitreal injection agreed wi th the profiles calculated from the mathematical model, together with the model parameters determined from the in vitro experiments. The pre sent in vivo/in vitro correlation, with the help of computer simulatio n, can be used for optimizing the therapeutic systems of intravitreal drug delivery.