Friedrich S W, Saville B A, Cheng Y L, Rootman D S
Department of1 Chemical Engineering and Applied Chemistry, University of Toronto, Canada.
J Ocul Pharmacol Ther. 1996 Spring;12(1):5-18. doi: 10.1089/jop.1996.12.5.
Controlled release ocular inserts have been found to increase the amount of drug which is absorbed into the aqueous humour when compared to eyedrops. Systemic absorption following delivery using a controlled release insert has been found to be dependent on the release rate of the insert. The objective of this study was to determine if ocular inserts affect drug absorption into other ocular tissues such as the conjunctiva and iris-ciliary body. Ocular absorption studies were performed using albino rabbits and ethylene-vinyl acetate controlled release devices containing timolol maleate. A compartmental model previously developed to simulate ocular absorption following eyedrop administration was modified and used to simulate these experiments. The conjunctival absorption coefficient calculated by the model and the AUC of the conjunctiva per mumol of delivered drug were found to be 2.7 and 42 times higher, respectively, for the ocular insert as compared to eyedrop administration. The increased conjunctiva absorption was likely the result of reduced tear mixing, which caused a high local concentration of timolol between the insert and the conjunctiva. The AUC of the iris-ciliary body per mumol of delivered drug was found to be 24 times higher for the ocular inserts as compared to eyedrop administration. The AUC of the iris-ciliary body was found to be 1.4 times higher than the AUC of the aqueous humour for eyedrop administration, but 9 times greater for delivery via the ocular inserts. Thus, the increased absorption into the iris-ciliary body and aqueous humour observed for ocular inserts is partially the result of an increase in the amount of drug which enters these tissues via penetration across the conjunctiva and sclera.
与眼药水相比，已发现控释眼用插入剂可增加吸收进入房水的药物量。使用控释插入剂给药后的全身吸收已发现取决于插入剂的释放速率。本研究的目的是确定眼用插入剂是否会影响药物吸收到其他眼组织中，如结膜和虹膜睫状体。使用白化兔和含有马来酸噻吗洛尔的乙烯-醋酸乙烯酯控释装置进行眼吸收研究。对先前开发的用于模拟眼药水给药后眼吸收的房室模型进行了修改，并用于模拟这些实验。与眼药水给药相比，模型计算出的结膜吸收系数以及每微摩尔给药药物的结膜AUC分别高出2.7倍和42倍。结膜吸收增加可能是泪液混合减少的结果，这导致插入剂与结膜之间的噻吗洛尔局部浓度较高。每微摩尔给药药物的虹膜睫状体AUC与眼药水给药相比，眼用插入剂高出24倍。对于眼药水给药，虹膜睫状体的AUC比房水的AUC高1.4倍，但对于通过眼用插入剂给药则高9倍。因此，眼用插入剂观察到的进入虹膜睫状体和房水的吸收增加部分是由于通过结膜和巩膜渗透进入这些组织的药物量增加的结果。
