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In this study, we developed a novel transdermal patch of alendronate, a nitrogen-containing bisphosphonate, for the treatment of bone diseases. The maximum permeation fluxes of alendronate through rat and human skin after application of this patch were 1.9 and 0.3\u2009\u00b5g\/cm2 per hour, respectively. The bioavailability (BA) of alendronate in rats was approximately 8.3% after the application of alendronate patch and approximately 1.7% after oral administration. These results indicated that the transdermal permeation of alendronate using this patch system was sufficient for the treatment of bone diseases. The plasma calcium level was effectively reduced after application of the alendronate patch in 1\u03b1-hydroxyvitamin D3\u2013induced hypercalcemia model rats. The alendronate patch also effectively suppressed the decrease in bone mass in model rats with osteoporosis. Modest alendronate-induced erythema of rat skin was observed after application of the alendronate patch. Incorporation of butylhydroxytoluene in the alendronate patch almost completely suppressed this alendronate-induced skin damage while maintaining the transdermal permeation and pharmacologic effects of alendronate. These findings indicate that our novel transdermal delivery system for alendronate is a promising approach to improve compliance and quality of life of patients in the treatment of bone diseases. \u00a9 2010 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.147","type":"journal-article","created":{"date-parts":[[2010,6,7]],"date-time":"2010-06-07T20:53:44Z","timestamp":1275944024000},"page":"2582-2591","source":"Crossref","is-referenced-by-count":44,"title":["Development of a novel transdermal patch of alendronate, a nitrogen-containing bisphosphonate, for the treatment of osteoporosis"],"prefix":"10.1093","volume":"25","author":[{"given":"Kosuke","family":"Kusamori","sequence":"first","affiliation":[{"name":"Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidemasa","family":"Katsumi","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuka","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-shu","family":"Quan","sequence":"additional","affiliation":[{"name":"CosMED Pharmaceutical Company, Ltd., Kamigyo-ku, Kyoto, Japan"},{"name":"Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumio","family":"Kamiyama","sequence":"additional","affiliation":[{"name":"CosMED Pharmaceutical Company, Ltd., Kamigyo-ku, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyasu","family":"Sakane","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,11,23]]},"reference":[{"key":"2024020320084124800_bib1","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/BF02555748","article-title":"Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat","volume":"38","author":"Schenk","year":"1986","journal-title":"Calcif Tissue Int."},{"key":"2024020320084124800_bib2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1097\/00003086-198704000-00009","article-title":"Experimental basis for the use of bisphosphonates in Paget's disease of bone","volume":"217","author":"Fleisch","year":"1987","journal-title":"Clin Orthop Relat Res."},{"key":"2024020320084124800_bib3","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1196\/annals.1365.036","volume":"1092","author":"Lambrinoudaki","year":"2006","journal-title":"Bisphosphonates. 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