{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T13:01:52Z","timestamp":1761310912949,"version":"build-2065373602"},"reference-count":11,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,12,26]],"date-time":"2013-12-26T00:00:00Z","timestamp":1388016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2014,2]]},"abstract":"Abstract<\/jats:title>\n\n\n\n\n\nPreclinical Research<\/jats:td>\n<\/jats:tr>\n<\/jats:tbody>\n<\/jats:table>\n\n<\/jats:table-wrap><\/jats:p>The purpose of this research work is to evaluate toxicity of diethylenetriamine pentaacetic acid zinc trisodium salt (Zn<\/jats:styled-content>\u2010DTPA<\/jats:styled-content>) tablets, a novel oral solid dosage form containing permeation enhancers in beagle dogs and S<\/jats:styled-content>prague D<\/jats:styled-content>awley rats. (Z<\/jats:styled-content>n\u2010DTPA<\/jats:styled-content>) in tablet dosage form was administered once daily for 7 days to beagle dogs at low (840\u2009mg\/dog\/day), mid (2520\u2009mg\/dog\/day), or high (7560\u2009mg\/dog\/day). On day 8, all treated and control groups were necropsied. The novel Z<\/jats:styled-content>n\u2010DTPA<\/jats:styled-content> tablet formulation showed rapid absorption with the Tmax<\/jats:sub> at 1\u2009h. Plasma concentrations as high as 270\u2009\u03bcg\/mL were observed after 7 days of administration. Exposure to DTPA<\/jats:styled-content>, based on area under the curve (A<\/jats:styled-content>UC<\/jats:styled-content>last<\/jats:sub>) and maximum concentration (C<\/jats:styled-content>max<\/jats:sub>), was dose dependent but not dose proportional. No biologically relevant changes in hematology or clinical chemistry that were related to DTPA<\/jats:styled-content> exposure were observed, and there were no changes in body weight in treated dogs compared with controls. Zn<\/jats:styled-content>\u2010DTPA<\/jats:styled-content> was well tolerated, with minor toxicological effects of emesis and diarrhea, following oral tablet administration for 7 consecutive days. Based on the endpoints evaluated in this study, the maximum tolerated dose is considered to be greater than 7560\u2009mg\/dog\/day (2535\u2009\u03bcmol\/kg\/day, 1325\u2009mg\/kg\/day), and the no\u2010observed\u2010adverse\u2010effect level (NOAEL<\/jats:styled-content>) is considered to be approximately 1325\u2009mg\/kg\/day per oral when given to male and female beagle dogs. For rats, the NOAEL<\/jats:styled-content> was estimated to be greater than 1000\u2009mg\/kg\/day when administered by oral gavage of the crushed Z<\/jats:styled-content>n\u2010DTPA<\/jats:styled-content> tablets as suspension once daily (qd) to male and female S<\/jats:styled-content>prague D<\/jats:styled-content>awley rats.<\/jats:p>","DOI":"10.1002\/ddr.21165","type":"journal-article","created":{"date-parts":[[2013,12,26]],"date-time":"2013-12-26T13:15:16Z","timestamp":1388063716000},"page":"37-46","source":"Crossref","is-referenced-by-count":16,"title":["Evaluating the Toxicity of Novel Z<\/scp>n\u2010DTPA<\/scp> Tablet Formulation in Dogs and Rats"],"prefix":"10.1002","volume":"75","author":[{"given":"Gita N.","family":"Shankar","sequence":"first","affiliation":[{"name":"SRI International Biosciences Division Menlo Park CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suresh","family":"Potharaju","sequence":"additional","affiliation":[{"name":"SRI International Biosciences Division Menlo Park CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol E.","family":"Green","sequence":"additional","affiliation":[{"name":"SRI International Biosciences Division Menlo Park CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,12,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1667\/RR1485.1"},{"key":"e_1_2_7_3_1","first-page":"439","article-title":"Toxicological study of DTPA as a Drug (III), Side effects of orally administered Zn\u2010DTPA to beagle dogs","volume":"22","author":"Fukuda S","year":"1987","journal-title":"JJHP"},{"key":"e_1_2_7_4_1","first-page":"115","article-title":"Toxicological study of DTPA as a Drug (V): Toxicities of Ca\u2010DTPA, Ca\u2010EDTA and CBMIDA after Intravenous injection in beagle dogs","volume":"25","author":"Fukuda S","year":"1990","journal-title":"JJHP"},{"key":"e_1_2_7_5_1","first-page":"101","article-title":"Toxicological study of DTPA as a Drug (IV), Side effects of orally administered Zn\u2010DTPA to beagle dogs","volume":"26","author":"Fukuda S","year":"1991","journal-title":"JJHP"},{"key":"e_1_2_7_6_1","first-page":"1","article-title":"Decorporation of radionuclides from the human body. Special issue","volume":"87","author":"Henge\u2010Napoli MH","year":"2000","journal-title":"Radiat Prot Dosimetry"},{"key":"e_1_2_7_7_1","unstructured":"NCRP National Council on Radiation Protection and Measurements.1980.Management of persons accidentally contaminated with radionuclides: handbook NCRP report no. 65. Bethesda MD."},{"key":"e_1_2_7_8_1","unstructured":"NCRP National Council on Radiation Protection and Measurements.2008.Management of persons contaminated with radionuclides: handbook NCRP Report no. 161. Bethesda MD."},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.2307\/3574122"},{"key":"e_1_2_7_10_1","unstructured":"ShankarGN ParishHJ.2011.Oral DTPA for radionuclide chelation. US Patent 7\u2009914\u2009767."},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21022"},{"volume-title":"Treatment of incorporated transuranium elements. IAEA technical report series no. 184","year":"1978","author":"Volf V","key":"e_1_2_7_12_1"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fddr.21165","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.21165","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T12:15:23Z","timestamp":1760357723000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.21165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,26]]},"references-count":11,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1002\/ddr.21165"],"URL":"https:\/\/doi.org\/10.1002\/ddr.21165","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"type":"print","value":"0272-4391"},{"type":"electronic","value":"1098-2299"}],"subject":[],"published":{"date-parts":[[2013,12,26]]}}}