Pharmacokinetic model for in vivo/in vitro correlation of intravitreal drug delivery.
A pharmacokinetic model of intravitreal drug delivery has been developed for describing the elimination and distribution of ocular drugs in the posterior segments of the eye. The model, based on Fick's second law of diffusion, assumes the cylindrical vitreous body with three major pathways for elimination: the posterior aqueous chamber, the retina/choroids/sclera (RCS) membrane and the lens posterior capsule. The model parameters such as the diffusion coefficient and the partition coefficient of the drug in the vitreous body and its surrounding tissues, the posterior lens capsule and the retina/choroids/sclera membrane, can be determined from in vitro membrane penetration experiments using respective rabbit tissues. The time course of in vivo mean concentration of the drug in the rabbit vitreous body following intravitreal drug delivery well agreed with the profile calculated from the present pharmacokinetic model for both membrane-controlled polymeric devices and biodegradable rod-matrix systems. The pharmacokinetic model suggests that the major route of elimination of drug molecules released from the vitreous implant is through the posterior aqueous humor because of the absence of a barrier membrane. However, the elimination through the RCS membrane cannot be overlooked because of the large diffusion area of the RCS membrane. The vitreous body concentration of the drug released from biodegradable vitreous implants can be predicted from the in vivo release rate-time profile by the present pharmacokinetic model.
Tojo
K
K
College of Computer Science and Systems Engineering, Kyushu Institute of Technology, Iizuka Campus, 820-8502, Fukuoka, Japan. tojo@bse.kyutech.ac.jp
Isowaki
A
A
D000818:Animals; D002829:Choroid / Q000378:metabolism; D004058:Diffusion; D006801:Humans; D008954:Models, Biological; D010539:Permeability; D010599:Pharmacokinetics; D012160:Retina / Q000378:metabolism; D012590:Sclera / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism*