Ohtori A, Tojo K
Department of Biochemical Science and Engineering, College of Computer Science and Biosystems Engineering, Kyushu Institute of Technology, Fukuoka, Japan.
Biol Pharm Bull. 1994 Feb;17(2):283-90. doi: 10.1248/bpb.17.283.
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.
在体内和体外条件下，测定了兔玻璃体腔内注射间磺基苯甲酸钠地塞米松（DMSB）后的消除情况。体内消除速率明显高于体外，这表明体内数据不仅包括玻璃体液中代谢/降解导致的消除，还包括通过周围组织（如后房水、视网膜/脉络膜/巩膜膜和晶状体）的消除。建立了一个基于菲克第二扩散定律的通用数学模型，用于描述玻璃体腔内注射DMSB的药代动力学。模型参数通过一组体外实验独立确定。玻璃体腔内注射DMSB后的体内消除数据与根据数学模型计算的曲线以及从体外实验确定的模型参数一致。借助计算机模拟，目前的体内/体外相关性可用于优化玻璃体腔内药物递送的治疗系统。
