{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T04:36:46Z","timestamp":1754109406042,"version":"3.28.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2000,9,1]],"date-time":"2000-09-01T00:00:00Z","timestamp":967766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>To enhance the ocular uptake of N-[4-(benzoylamino)phenylsulfonyl]glycine (BAPSG), two ester (methyl and isopropyl) prodrugs were synthesized and evaluated for their stability in various buffers (pH 1\u20139), hydrolysis in rabbit ocular tissues (cornea, conjunctiva, iris-ciliary body, lens, aqueous humor, and vitreous humor), transport across cornea and conjunctiva, and in-vivo uptake following topical administration.<\/jats:p>\n               <jats:p>Lipophilic ester prodrugs of BAPSG showed good aqueous solution stability in tissue homogenates. However, these prodrugs lacking the free carboxylate anion exhibited reduced in-vitro permeability and in-vivo uptake, suggesting the importance of free carboxylate anion in the delivery of BAPSG.<\/jats:p>\n               <jats:p>Over the pH range of 1\u20139, the rate constants for degradation ranged from 5.67 to 218.9 times 10\u22123 h\u22121 for the methyl ester and from 3.14 to 4.45 times 10\u22123 h\u22121 for the isopropyl ester. At all pH conditions, the isopropyl ester was more stable when compared with the methyl ester. A change in buffer concentration at pH 7.4 did not influence the stability of the prodrugs. The prodrugs were rapidly hydrolysed in the tissue homogenates, with the rate constants for hydrolysis ranging from 1.98 to 7.2 times 10\u22123 min\u22121 for the methyl ester and 3.32 to 6.53 times 10\u22123 min\u22121 for the isopropyl ester. The in-vitro permeability of the methyl ester was less than the parent drug across cornea and conjunctiva. Isopropyl ester levels were not detectable in the receiver chamber even at the end of the 4-h transport study. Following topical administration of BAPSG and the two prodrugs at a dose of 60 \u03bcg\/eye, the lowest levels were seen in vitreous humor for parent compound and its methyl ester. In general, the tissue uptake of methyl ester was less than BAPSG. Isopropyl ester levels were below detection limits in all the ocular tissues.<\/jats:p>","DOI":"10.1211\/0022357001774877","type":"journal-article","created":{"date-parts":[[2003,7,18]],"date-time":"2003-07-18T23:43:52Z","timestamp":1058571832000},"page":"1113-1122","source":"Crossref","is-referenced-by-count":7,"title":["In-vitro Hydrolysis, Permeability, and Ocular Uptake of Prodrugs of <i>N<\/i>-[4-(Benzoylamino)phenylsulfonyl]glycine, a Novel Aldose Reductase Inhibitor"],"prefix":"10.1093","volume":"52","author":[{"given":"Gangadhar","family":"Sunkara","sequence":"first","affiliation":[{"name":"College of Pharmacy, University of Nebraska Medical Center , Omaha, NE 68198-6025,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"DeRuiter","sequence":"additional","affiliation":[{"name":"Department of Pharmacal Sciences, Auburn University , Auburn, AL 36849-5503,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C Randall","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Pharmacal Sciences, Auburn University , Auburn, AL 36849-5503,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uday B","family":"Kompella","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Nebraska Medical Center , Omaha, NE 68198-6025,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,9,1]]},"reference":[{"key":"2024103110055131500_cit1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0014-4835(84)90102-7","article-title":"Comparison of the ocular hypotensive efficacy of eicosanoids and related compounds","volume":"38","author":"Bito","year":"1984","journal-title":"Exp. 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