{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T17:57:09Z","timestamp":1789927029663,"version":"4.0.1"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T00:00:00Z","timestamp":1415750400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T00:00:00Z","timestamp":1415750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:italic>Introduction<\/jats:italic> Aldoxorubicin, a prodrug of doxorubicin, binds covalently to serum albumin in the bloodstream and accumulates in tumors. Aldoxorubicin can be administered at doses several-fold higher than doxorubicin can, without associated acute cardiotoxicity. <jats:italic>Purpose<\/jats:italic> This study fully evaluated the pharmacokinetic profile of aldoxorubicin (serum and urine). <jats:italic>Methods<\/jats:italic> Eighteen patients with advanced solid tumors received aldoxorubicin 230 or 350\u00a0mg\/m<jats:sup>2<\/jats:sup> (equivalent in drug load to doxorubicin at doses of 170 or 260\u00a0mg\/m<jats:sup>2<\/jats:sup>, respectively) once every 21\u00a0days. Blood samples were taken in cycle 1 before aldoxorubicin infusion, and at 5, 15, 30, and 60\u00a0min, and at 2, 4, 8, 12, 16, 24, 48, and 72\u00a0h after infusion. Urine samples were taken in cycle 1 at 24, 48, and 72\u00a0h after infusion. Limited blood sampling was done in cycle 3, before aldoxorubicin infusion, and at 60\u00a0min and at 2, 4, and 8\u00a0h after infusion. <jats:italic>Results<\/jats:italic> The long mean half-life (20.1\u201321.1\u00a0h), narrow mean volume of distribution (3.96\u20134.08\u00a0L\/m<jats:sup>2<\/jats:sup>), and slow mean clearance rate (0.136\u20130.152\u00a0L\/h\/m<jats:sup>2<\/jats:sup>) suggest that aldoxorubicin is stable in circulation and does not accumulate readily in body compartments outside of the bloodstream. Very little doxorubicin and its major metabolite doxorubicinol, which has been implicated in doxorubicin-associated cardiotoxicity, are excreted in urine. This might explain the lack of cardiotoxicity observed thus far with aldoxorubicin. <jats:italic>Conclusions<\/jats:italic> Our findings support dosing and administration schemas used in an ongoing phase 3 clinical study of aldoxorubicin in soft tissue sarcoma, and phase 2 clinical studies in small cell lung cancer, glioblastoma, and Kaposi\u2019s sarcoma.<\/jats:p>","DOI":"10.1007\/s10637-014-0183-5","type":"journal-article","created":{"date-parts":[[2014,11,14]],"date-time":"2014-11-14T22:20:02Z","timestamp":1416003602000},"page":"341-348","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Pharmacokinetic study of aldoxorubicin in patients with solid tumors"],"prefix":"10.1007","volume":"33","author":[{"given":"Monica M.","family":"Mita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald B.","family":"Natale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M.","family":"Wolin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Laabs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillary","family":"Dinh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Wieland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Levitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain C.","family":"Mita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,11,12]]},"reference":[{"key":"183_CR1","unstructured":"Doxorubicin hydrochloride [prescribing information] (2010) Bedford, OH: Bedford Laboratories"},{"key":"183_CR2","unstructured":"National Cancer Institute (2013) Cancer drug information: Doxorubicin hydrochloride. http:\/\/www.cancer.gov\/cancertopics\/druginfo\/doxorubicinhydrochloride\/print. 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