{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T16:46:22Z","timestamp":1761929182660},"reference-count":14,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T00:00:00Z","timestamp":1362700800000},"content-version":"vor","delay-in-days":3903,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:p>Didanosine is an acid labile drug and hence has been given with buffering agents. To avoid the need for concurrent administration with antacids, an encapsulated enteric\u2010coated bead formulation of didanosine was developed. The objective of this study was to assess the bioequivalence of the encapsulated enteric\u2010coated beads compared to the buffered tablet. Two separate open\u2010label, randomized, two\u2010way crossover studies were conducted, one in healthy subjects and the other in HIV\u2010infected subjects (with CD4 cell counts &gt; 200 cells\/mm<jats:sup>3<\/jats:sup>). All subjects received a 400\u2010mg dose of the buffered tablet (reference formulation) and the encapsulated enteric\u2010coated beads (test formulation). Blood samples were collected over 12 hours, and plasma levels of didanosine were determined using a validated assay. The 90% confidence interval (CI) of the ratio of the geometric means of log\u2010transformed C<jats:sub>max<\/jats:sub> and AUC<jats:sub>\u221e<\/jats:sub> values were used to assess bioequivalence between the two formulations using the equivalence interval of 0.80 and 1.25. In healthy volunteers (n = 46), the point estimate and 90% CI of the ratios of C<jats:sub>max<\/jats:sub> and AUC<jats:sub>\u221e<\/jats:sub> values were 0.58 (0.52, 0.64) and 1.02 (0.95, 1.01), respectively. In HIV\u2010infected subjects (n = 30), the point estimate and 90% CI of the ratios of C<jats:sub>max<\/jats:sub> and AUC<jats:sub>\u221e<\/jats:sub> values were 0.64 (0.56, 0.72) and 0.95 (0.86, 1.06), respectively. Median t<jats:sub>max<\/jats:sub> value increased significantly from 0.67 hours for the buffered tablet in both studies to 2.33 hours (in healthy subjects) or 2.0 hours (in HIV\u2010infected subjects) for the enteric\u2010coated beads. The mean half\u2010life of didanosine was similar between treatments and ranged between 1.60 and 1.70 hours across healthy and HIV\u2010infected subjects. It was concluded that the encapsulated enteric\u2010coated bead formulation of didanosine is equivalent to the buffered tablet in the extent of exposure but differs in the rate of absorption. The pharmacokinetic profile of the enteric formulation appears to be similar in healthy and HIV\u2010infected subjects.<\/jats:p>","DOI":"10.1177\/009127002401102623","type":"journal-article","created":{"date-parts":[[2003,7,19]],"date-time":"2003-07-19T09:38:13Z","timestamp":1058607493000},"page":"791-797","source":"Crossref","is-referenced-by-count":20,"title":["Bioequivalence of Two Formulations of Didanosine, Encapsulated Enteric\u2010Coated Beads and Buffered Tablet, in Healthy Volunteers and HIV\u2010Infected Subjects"],"prefix":"10.1002","volume":"42","author":[{"given":"Bharat D.","family":"Damle","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjeev","family":"Kaul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Behr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Knupp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,8]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5173(88)90031-2"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.2.385-391.2002"},{"issue":"2","key":"e_1_2_1_4_2","first-page":"E97","article-title":"Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose\u2010response curves","volume":"235","author":"DeLean A","year":"1978","journal-title":"American Journal of Physiology"},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1201\/b14095","volume-title":"Pharmacokinetics.","author":"Gibaldi M","year":"1982"},{"key":"e_1_2_1_6_2","volume-title":"SAS\/STAT\u00ae User's Guide.","author":"SAS Institute","year":"1997"},{"key":"e_1_2_1_7_2","unstructured":"KnuppC UllahI WileyG DennisA DollW SandeferE:Evaluation of two enteric coated formulations of didanosine using pharmacokinetics and \u03b3;\u2010scintigraphy in healthy male subjects [abstract 1663]. Paper presented at the 40th annual ICAAC meeting Toronto Canada September 2000."},{"key":"e_1_2_1_8_2","first-page":"431","article-title":"Factors determining the activity of 2\u2032,3\u2032\u2010dideoxynucleosides in suppressing human immunodeficiency virus in vitro","volume":"34","author":"Zhang H","year":"1988","journal-title":"Molecular Pharmacology"},{"key":"e_1_2_1_9_2","first-page":"369","article-title":"Anomalous accumulation and decay of 2\u2032,3\u2032\u2010 dideoxyadenosine\u20105\u2032\u2010triphosphate in human T\u2010cell cultures exposed to the anti\u2010HIV drug 2\u2032,3\u2032\u2010dideoxyinosine","volume":"21","author":"Ahluwalia G","year":"1993","journal-title":"Drug Metabolism and Disposition"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/16.Supplement_1.S26"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/165.1.99"},{"key":"e_1_2_1_12_2","unstructured":"SchraderS SharmaS SeekinsD McGovernR ConnaughtonE HoffmanE et al:Comparison of HIV RNA suppression produced by triple regimens containing either didanosine enteric\u2010coated or didanosine tablet formulations each administered once daily [abstract 318]. Paper presented at the 8th Conference on Retrovirus and Opportunistic Infections Chicago February 2001."},{"key":"e_1_2_1_13_2","unstructured":"BadereoR GatheJ GrimwoodA KlesczewskiK McLarenC:Evaluation of a triple combination regimen containing enteric coated didanosine administered once daily [abstract 57]. Paper presented at the First IAS Conference on HIV Pathogenesis and Treatment Buenos Aires Argentina July 2001."},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00637752"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199936010-00004"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1177%2F009127002401102623","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/009127002401102623","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T12:46:53Z","timestamp":1700398013000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1177\/009127002401102623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,7]]},"references-count":14,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2002,7]]}},"alternative-id":["10.1177\/009127002401102623"],"URL":"https:\/\/doi.org\/10.1177\/009127002401102623","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,7]]}}}