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    Sulfobutyl Ether b-Cyclodextrin (SBE-b-CD) in Eyedrops Improves the Tolerability of a Topically Applied Pilocarpine Prodrug in Rabbits

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    Issue Date
    1995
    Author
    Stella, Valentino J.
    Järvinen, Tomi
    Järvinen, Kristina
    Thompson, Diane
    Urtti, Arto
    Publisher
    Mary Ann Leibert
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
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    Abstract
    The effects of a novel, modified β-cyclodextrin (SBE4-β-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 (Imax) and increased the time to reach peak (tmax), but did not significantly affect values for the area under the miosis versus time curves (AUC), 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-β-CD significantly decreased the eye irritation of the pilocarpine prodrug solutions. Coadministered SBE4-β-CD did not affect the miotic response of prodrug solution when the molar ratio of SBE4-β-CD to prodrug was low. However, increasing the molar ratio of SBE4-β-CD to prodrug decreased the Imax and AUC values. The results show that eye irritation of the pilocarpine prodrug is prevented by levels of SBE4-β-CD that do not affect the apparent ocular absorption of the prodrug.
    Description
    This is the publisher's version, also available electronically from http://dx.doi.org/10.1089/jop.1995.11.95
    URI
    http://hdl.handle.net/1808/8106
    DOI
    https://doi.org/10.1089/jop.1995.11.95
    Collections
    • Distinguished Professors Scholarly Works [918]
    • Pharmaceutical Chemistry Scholarly Works [336]
    Citation
    Sulfobutyl Ether b-Cyclodextrin (SBE-b-CD) in Eyedrops Improves the Tolerability of a Topically Applied Pilocarpine Prodrug in Rabbits, T. Jarvinen, K. Jarvinen, A. Urtti, D. Thompson and V. J. Stella, J. Ocul. Pharmacol. Ther., 11, 95-106 (1995). http://dx.doi.org/10.1089/jop.1995.11.95

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    KU Libraries
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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