In vivo/in vitro correlation of intravitreal delivery of drugs with the help of computer simulation.
The elimination of dexamethasone sodium m-sulfobenzoate, DMSB, following intravitreal injection, was measured in rabbit vitreous body under in vivo and in vitro conditions. The rate of elimination in vivo was appreciably greater than that in vitro, indicating that the in vivo data include not only the elimination due to metabolism/degradation in the vitreous humor, but also the elimination through the surrounding tissues such as the posterior aqueous humor, the retina/choroid/sclera membrane, and the lens. A general mathematical model based on Fick's second law of diffusion was developed for describing the pharmacokinetics of the intravitreal injection of DMSB. The model parameters were independently determined from a set of in vitro experiments. The in vivo data of elimination of DMSB following intravitreal injection agreed with the profiles calculated from the mathematical model, together with the model parameters determined from the in vitro experiments. The present in vivo/in vitro correlation, with the help of computer simulation, can be used for optimizing the therapeutic systems of intravitreal drug delivery.
Ohtori
A
A
Department of Biochemical Science and Engineering, College of Computer Science and Biosystems Engineering, Kyushu Institute of Technology, Fukuoka, Japan.
Tojo
K
K
D000818:Animals; D002829:Choroid / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D004058:Diffusion; D005123:Eye / Q000378:metabolism*; D066298:In Vitro Techniques; D007903:Lens Capsule, Crystalline / Q000378:metabolism; D011355:Prodrugs / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D011817:Rabbits; D012160:Retina / Q000378:metabolism; D012590:Sclera / Q000378:metabolism; D014018:Tissue Distribution; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism*
D011355:Prodrugs; C079704:dexamethasone-21-sulfobenzoate; D003907:Dexamethasone