{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:16:38Z","timestamp":1792059398966,"version":"4.4.0"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vonoprazan is a new potassium\u2010competitive acid blocker to treat acid\u2010related diseases. However, its safety during pregnancy is unclear. The aim of the study was to investigate the potential reproductive toxicity on the embryo\u2013fetal development of vonoprazan. Vonoprazan acetate was administered by intravenous injection to pregnant rats (0, 2, 6 and 20\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup> day<jats:sup>\u20131<\/jats:sup>) and rabbits (0, 1.2, 3.6 and 12\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup> day<jats:sup>\u20131<\/jats:sup>) during the organogenetic period (gestation day 6\u201315 [rats] and 6\u201318 [rabbits]). Maternal reproductive endpoints were evaluated, together with effects on fetal growth and morphological development. In rats, no treatment\u2010related effects were found in the highest dose group (20\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup>) and the maternal plasma exposure was \u226550\u2010fold the expected clinical human exposure. However, in rabbits, dose\u2010related clinical signs (soft or liquid feces) occurred in the 12\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup> group, which was regarded as a maternal toxicity. Besides, decreased maternal weight gain also was considered as a minimal maternal toxicity. At 12\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup>, delayed fetal ossification was found as evidence of embryo\u2013fetal growth retardation, which was related to decreased fetal and placental weights. There was no maternal and developmental toxicity in the 1.2 and 3.6\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup> groups. Thus, the no\u2010observed\u2010adverse\u2010effect levels of vonoprazan acetate in rabbits are considered 3.6\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup> day<jats:sup>\u20131<\/jats:sup>, which produced plasma exposure that was about 18\u2010fold human clinical exposure.<\/jats:p>","DOI":"10.1002\/jat.3607","type":"journal-article","created":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T11:57:39Z","timestamp":1523879859000},"page":"987-995","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Embryo\u2013fetal toxicity assessment of vonoprazan in rats and rabbits"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0797-8955","authenticated-orcid":false,"given":"Tianyi","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Nanjing Tech University  Nanjing 211816 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3460-0883","authenticated-orcid":false,"given":"Hongqun","family":"Qiao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Nanjing Tech University  Nanjing 211816 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4619-7748","authenticated-orcid":false,"given":"Peng","family":"Yue","sequence":"additional","affiliation":[{"name":"JiangSu Center for Safety Evaluation of Drugs  Nanjing 211816 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6179-3855","authenticated-orcid":false,"given":"Ming","family":"Cai","sequence":"additional","affiliation":[{"name":"JiangSu Center for Safety Evaluation of Drugs  Nanjing 211816 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9191-2050","authenticated-orcid":false,"given":"Xuejun","family":"He","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Nanjing Tech University  Nanjing 211816 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2007.05.006"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2007.12.001"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/10520292609115636"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2011.04.008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0326-7"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0368-z"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.170274"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.179556"},{"key":"e_1_2_8_10_1","unstructured":"ICH. 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