SULFOBUTYL ETHER BETA-CYCLODEXTRIN (SBE-BETA-CD) IN EYEDROPS IMPROVES THE TOLERABILITY OF A TOPICALLY APPLIED PILOCARPINE PRODRUG IN RABBITS

被引：47

作者：

JARVINEN, T ^{[1
]}

JARVINEN, K ^{[1
]}

URTTI, A ^{[1
]}

THOMPSON, D ^{[1
]}

STELLA, VJ ^{[1
]}

机构：

[1] UNIV KANSAS,DEPT PHARMACEUT CHEM,LAWRENCE,KS 66045

来源：

JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS | 1995年 / 11卷 / 02期

关键词：

D O I：

10.1089/jop.1995.11.95

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

The effects of a novel, modified p-cyclodextrin (SBE4-beta-CD; a variably substituted sulfobutyl ether with an average degree of substitution of four) on eye irritation and miotic response of an ophthalmically applied pilocarpine prodrug, O,O'-dipropionyl-(1,4-xylylene) bispilocarpate, in albino rabbits were studied. Compared to the commercial pilocarpine eyedrop solution (163 mM, equivalent to 3.4% pilocarpine), 12 - 24 mM pilocarpine prodrug solutions (equivalent to 0.5 1.0% pilocarpine, respectively) decreased peak miotic intensity (I-max) and increased the time to reach peak (t(max)), but did not significantly affect values for the area under the miosis versus time curves (AUG), i.e. 12 - 24 mM pilocarpine prodrug appeared to be equivalent to 163 mM pilocarpine. Ocularly applied 12 - 24 mM pilocarpine prodrug solutions, however, were more irritating than a commercial pilocarpine eyedrop solution. Coadministered SBE4-beta-CD significantly decreased the eye irritation of the pilocarpine prodrug solutions. Coadministered SBE4-beta-CD did not affect the miotic response of prodrug solution when the molar ratio of SBE4-beta-CD to prodrug was low. However, increasing the molar ratio of SBE4-beta-CD to prodrug decreased the I-max and AUC values. The results show that eye irritation of the pilocarpine prodrug is prevented by levels of SBE4-beta-CD that do not affect the apparent ocular absorption of the prodrug.

引用

页码：95 / 106

页数：12

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